Curated Optogenetic Publication Database

Abstract: T-cell activation is a highly regulated process requiring both antigen recognition via the T-cell receptor (TCR) and co-stimulatory signaling, notably through the co-stimulatory receptor CD28. Here, we introduce an optogenetic platform for reversible and tunable full activation of human T cells that does not require genetic modification. We engineered opto-CD28-REACT, a recombinant protein comprising an anti-CD28 single-chain variable fragment, GFP, and phytochrome-interacting factor 6 (PIF6). This construct binds CD28 and thereby attaches PIF6 to CD28. Upon red light (630 nm) illumination, PIF6 binds to PhyB tetramer-coated beads, triggering CD28 signaling that can be attenuated by far-red light (780 nm) in 2 min. We show that opto-CD28-REACT synergizes with opto-CD3ϵ-REACT-a complementary optogenetic tool targeting the TCR complex-to induce light-dependent activation of both Jurkat cells and primary human T cells. Co-stimulation through both opto-REACT systems promotes ERK phosphorylation, upregulation of the activation markers CD69 and CD25, interleukin-2 (IL-2) secretion, and T-cell proliferation, reaching levels similar to conventional antibody-mediated stimulation. This strategy enables precise optical control over TCR and CD28 signaling in non-genetically modified T cells, offering a powerful approach for dissecting the regulatory dynamics of T-cell activation and advancing applications in synthetic immunology.

Abstract: Over the past two decades, optogenetics has evolved from a conceptual framework into a powerful and versatile technology for controlling cellular processes with light. Rooted in the discovery and characterization of natural photoreceptors, the field has advanced through the development of genetically encoded, light-sensitive proteins that enable precise spatiotemporal control of ion flux, intracellular signaling, gene expression, and protein interactions. This review traces key milestones in the emergence of optogenetics and highlights the development of major optogenetic tools. From the perspective of genetic tool innovation, the focus is on how these tools have been engineered and optimized for novel or enhanced functions, altered spectral properties, improved light sensitivity, subcellular targeting, and beyond. Their broadening applications are also explored across neuroscience, cardiovascular biology, hematology, plant sciences, and other emerging fields. In addition, current trends such as all-optical approaches, multiplexed control, and clinical translation, particularly in vision restoration are discussed. Finally, ongoing challenges are addressed and outline future directions in optogenetic tool development and in vivo applications, positioning optogenetics as a transformative platform for basic research and therapeutic advancement.

Abstract: Optogenetically regulated enzymes offer unprecedented spatiotemporal control over protein activity, intermolecular interactions, and intracellular signaling. Many design strategies have been developed for their fabrication based on the principles of intrinsic allostery, oligomerization or 'split' status, intracellular compartmentalization, and steric hindrance. In addition to employing photosensory domains as part of the traditional optogenetic toolset, the specificity of effector domains has also been leveraged for endogenous applications. Here, we discuss the dynamics of light activation while providing a bird's eye view of the crafting approaches, targets, and impact of optogenetic enzymes in orchestrating cellular functions, as well as the bottlenecks and an outlook into the future.

Abstract: Phytochromes are photoreceptors sensitive to red and far-red light, found in a wide variety of organisms, including plants, fungi, and bacteria. Bacteriophytochromes (BphPs) can be switched between a red light-sensitive Pr state and a far-red light-sensitive Pfr state by illumination. In so-called prototypical BphPs, the Pr state functions as the thermally favored resting state, whereas Pfr is more stable in bathy BphPs. The prototypical DrBphP from Deinococcus radiodurans has been shown to be compatible with different output module types. Even though red light-regulated optogenetic tools are available, like the pREDusk system based on the DrBphP photosensory module, far-red light-modulated variants are still rare. Here, we study the underlying contributors to bathy over prototypical BphP behavior by way of various chimeric constructs between pREDusk and representative bathy BphPs. We pinpoint shared traits of the otherwise heterogeneous subgroup of bathy BphPs and highlight the importance of the sensor-effector linker in light modulation of histidine kinase activity. Informed by these data, we introduce the far-red light-activated system "pFREDusk", based on a histidine kinase activity governed by a bathy photosensory module. With this tool, we expand the optogenetic toolbox into wavelengths of increased sample and tissue penetration.

Abstract: Neurodegenerative diseases involve toxic protein aggregation. Recent evidence suggests that biomolecular phase separation, a process in which proteins and nucleic acids form dynamic, liquid-like condensates, plays a key role in this aggregation. Optogenetics, originally developed to control neuronal activity with light, has emerged as a powerful tool to investigate phase separation in living systems. This is achieved by fusing disease-associated proteins to light-sensitive oligomerization domains, enabling researchers to induce or reverse condensate formation with precise spatial and temporal control. This review highlights how optogenetic systems such as OptoDroplet are being used to dissect the mechanisms of neurodegenerative disease. We examine how these tools have been applied in models of neurodegenerative diseases, such as amyotrophic lateral sclerosis, Alzheimer's, Parkinson's, and Huntington's disease. These studies implicate small oligomeric aggregates as key drivers of toxicity and highlight new opportunities for therapeutic screening. Finally, we discuss advances in light-controlled dissolution of condensates and future directions for applying optogenetics to combat neurodegeneration. By enabling precise, dynamic control of protein phase behavior in living systems, optogenetic approaches provide a powerful framework for elucidating disease mechanisms and informing the development of targeted therapies.

Abstract: Early detection of pollutants in water discharge is an integral part of environmental monitoring. Electroactive biofilm (EAB)-enabled, microbial fuel cell (MFC)-based biosensors facilitate self-powered online pollutant detection. However, as EABs are highly dynamic, naturally formed EABs as sensing and transducing elements limit the performance of MFC-based biosensors. Here, we report a fast-response and sensitive MFC-based biosensor enabled by enhancing Shewanella oneidensis biofilms on the electrode using an optogenetic approach. We incorporated a near-infrared (NIR) light-responsive synthetic bis(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) module into S. oneidensis to promote biofilm formation on the anode under NIR light. The biosensors with enhanced EABs exhibited a rapid and sensitive response to Cr(VI), reducing the sensing time from approximately 30 min to just 3 min. This improved sensing performance was maintained over three sensing cycles, even with fluctuating Cr(VI) concentrations. Based on the analyses of the electrode biofilms and extracellular polymeric substance matrices, different Cr(VI) response mechanisms for the normal and enhanced EABs were proposed; enhanced EAB's massive dispersal by Cr(VI) was the cause of the improved response of the biosensors. Such improved response still held in the natural water matrix. This proof-of-concept study provides valuable insights into controlling electrode biofilm dynamics for the rapid and robust early detection of pollutants using MFC-based biosensors.

Abstract: Nanobodies, the camelid-derived single-chain variable domain of heavy-chain-only antibodies, are compact in size and exhibit high binding affinity and specificity to their binding partners. As innovative antibody modalities, nanobodies have garnered significant attention in medicine and biological research. To achieve higher spatiotemporal precision, nanobody-based light-controlled systems-such as photobody, optobody, photoactivatable nanobody conjugate inducers of dimerization, and others-have been developed. These systems enable optical control of biological processes while leveraging the advantages of nanobodies as a binding moiety. This concept, summarizes nanobody-based photoregulated systems for investigating biology through light, highlights their advantages and potential limitations, and discusses future directions in this emerging research area.

Abstract: Microbial optogenetic tools can regulate gene expression with high spatial and temporal precision, offering excellent potential for single-cell resolution studies. However, bacterial optogenetic systems have primarily been deployed for population-level experiments. It is not always clear how these tools perform in single cells, where stochastic effects can be substantial. In this study, we focus on optogenetic Cre recombinase and systematically compare the performance of three variants (OptoCre-REDMAP, OptoCre-Vvd, and PA-Cre) for their population-level and single-cell activity. We quantify recombination efficiency, expression variability, and activation dynamics using reporters which produce changes in fluorescence or antibiotic resistance following light-induced Cre activity. Our results indicate that optogenetic recombinase performance can be reporter-dependent, suggesting that this is an important consideration in system design. Further, our single-cell analysis reveals highly heterogeneous activity across cells. Although general trends match expectations for mean levels of light-dependent recombination, we found substantial variation in this behavior across individual cells. In addition, our results show that the timing of recombinase activity is highly variable from cell to cell. These findings suggest critical criteria for selecting appropriate optogenetic recombinase systems and indicate areas for optimization to improve the single-cell capabilities of bacterial optogenetic tools.

Abstract: Light-inducible regulatory proteins are powerful tools to interrogate fundamental mechanisms driving cellular behavior. In particular, genetically encoded photosensory domains fused to split proteins can tightly modulate protein activity and gene expression. While light-inducible split protein systems have performed well individually, few multichromatic and orthogonal gene regulation systems exist in mammalian cells. The design space for multichromatic circuits is limited by the small number of orthogonally addressable optogenetic switches and the types of effectors that can be actuated by them. We developed a library of red light-inducible recombinases and directed patterned myogenesis in a mesenchymal fibroblast-like cell line. To address the limited number of light-inducible domains (LIDs) responding to unique excitation spectra, we multiplexed light-inducible recombinases with our "Boolean logic and arithmetic through DNA excision" (BLADE) platform. Multiplexed optogenetic tools will be transformative for understanding the role of multiple interacting genes and their spatial context in endogenous signaling networks.

Abstract: Light is a critical environmental factor that governs the growth and development of plants. Plants have specialised photoreceptor proteins, which allow them to sense both quality and quantity of light and drive a wide range of responses critical for optimising growth, resource use and adaptation to changes in environment. Understanding the role of these photoreceptors in plant biology has opened up potential avenues for engineering crops with enhanced productivity by engineering photoreceptor activity and/or action. The ability to manipulate plant genomes through genetic engineering and synthetic biology approaches offers the potential to unlock new agricultural innovations by fine-tuning photoreceptors or photoreceptor pathways that control plant traits of agronomic significance. Additionally, optogenetic tools which allow for precise, light-triggered control of plant responses are emerging as powerful technologies for real-time manipulation of plant cellular responses. As these technologies continue to develop, the integration of photoreceptor engineering and optogenetics into crop breeding programs could potentially revolutionise how plant researchers tackle challenges of plant productivity. Here we provide an overview on the roles of key photoreceptors in regulating agronomically important traits, the current state of plant photoreceptor engineering, the emerging use of optogenetics and synthetic biology, and the practical considerations of applying these approaches to crop improvement. This review seeks to highlight both opportunities and challenges in harnessing photoreceptor engineering approaches for enhancing plant productivity. In this review, we provide an overview on the roles of key photoreceptors in regulating agronomically important traits, the current state of plant photoreceptor engineering, the emerging use of optogenetics and synthetic biology, and the practical considerations of applying these approaches to crop improvement.

Abstract: Red light, characterized by superior tissue penetration and minimal phototoxicity, represents an ideal wavelength for optogenetic applications. However, the existing tools for reversible protein inhibition by red light remain limited. Here, we introduce R-LARIAT (red light-activated reversible inhibition by assembled trap), a novel optogenetic system enabling precise spatiotemporal control of protein function via 660 nm red-light-induced protein clustering. Our system harnesses the rapid and reversible binding of engineered light-dependent binders (LDBs) to the bacterial phytochrome DrBphP, which utilizes the endogenous mammalian biliverdin chromophore for red light absorption. By fusing LDBs with single-domain antibodies targeting epitope-tagged proteins (e.g., GFP), R-LARIAT enables the rapid sequestration of diverse proteins into light-responsive clusters. This approach demonstrates high light sensitivity, clustering efficiency, and sustained stability. As a proof of concept, R-LARIAT-mediated sequestration of tubulin inhibits cell cycle progression in HeLa cells. This system expands the optogenetic toolbox for studying dynamic biological processes with high spatial and temporal resolution and holds the potential for applications in living tissues.

Abstract: Bacterial therapy has emerged as a promising approach for disease treatment due to its environmental sensitivity, immunogenicity, and modifiability. However, the clinical application of engineered bacteria is limited by differences of expression levels in patients and possible off-targeting. Optogenetics, which combines optics and genetics, offers key advantages such as remote controllability, non-invasiveness, and precise spatiotemporal control. By utilizing optogenetic tools, the behavior of engineered bacteria can be finely regulated, enabling on-demand control of the dosage and location of their therapeutic products. In this review, we highlight the latest advancements in the optogenetic engineering of bacteria for light-controlled disease theranostics and therapeutic regulation. By constructing a three-dimensional analytical framework of “sense-produce-apply”, we begin by discussing the key components of bacterial optogenetic systems, categorizing them based on their photosensitive protein response to blue, green, and red light. Next, we introduce innovative light-producing tools that extend beyond traditional light sources. Then, special emphasis is placed on the biomedical applications of optogenetically engineered bacteria in treating diseases such as cancer, intestinal inflammation and systemic disease regulation. Finally, we address the challenges and future prospects of bacterial optogenetics, outlining potential directions for enhancing the safety and efficacy of light-controlled bacterial therapies. This review aims to provide insights and strategies for researchers working to advance the application of optogenetically engineered bacteria in drug delivery, precision medicine and therapeutic regulation.

Abstract: Optogenetics is an interdisciplinary field wherein optical and genetic engineering methods are employed together to impart photounresponsive cells (usually of higher animals) the ability to respond to light through expression of light-sensitive proteins sourced generally from algae or bacteria. It enables precise spatiotemporal control of various cellular activities through light stimulation. Recently, emerging as a synthetic biology-based approach for diabetes management, optogenetics can provide user-control of hormonal secretion by photoactivation of a suitably modified cell. For around a decade, studies have been performed on the applicability of various light-sensitive proteins and their incorporation into pancreatic and nonpancreatic cells for photoinduced insulin secretion. Further, in vivo studies demonstrated amelioration of diabetes in mouse models through photoactivation of the implanted engineered cells. Here, we attempt to highlight the various optogenetic approaches explored in terms of influencing the insulin secretion pathway at different points in light of the natural insulin secretion pathway in pancreatic β cells. We also discuss how transgenic cells of both pancreatic as well as nonpancreatic origin are exploited for photoinduced secretion of insulin. Recent advances on integration of “smart” technologies for remote control of light irradiation and thereby insulin secretion from implanted engineered cells in preclinical models are also described. Additionally, the need for further comprehensive studies on irradiation parameters, red-shifted opsins, and host–cell interaction is stressed to realize the full potential of optogenetics as a clinically applicable modality providing user-controlled “on demand” hormonal secretion for better management of diabetes.

Abstract: Near-infrared (NIR) fluorescent proteins and optogenetic tools derived from bacterial phytochromes' photosensory core modules (PCMs) operate within the first (NIR-I) tissue transparency window under single-photon activation. Leveraging two-photon (2P) light in the second transparency window (NIR-II) for photoswitching bacterial phytochromes between Pr and Pfr absorption states offers significant advantages, including enhanced tissue penetration, spatial resolution, and signal-to-noise ratio. However, 2P photoconversion of bacterial phytochromes remains understudied. Here, we study the non-linear Pr to Pfr photoconversion's dependence on irradiation wavelength (1180–1360 nm) and energy fluence (41–339 mJ/cm2) for the PCM of DrBphP bacterial phytochrome. Our findings reveal substantially higher photoconversion efficiency for the engineered monomeric DrBphP-PCM (73%) compared to the natural dimeric DrBphP-PCM (57%). Molecular mechanical calculations, based on experimentally determined 2P absorption cross-section coefficients for the monomer (167 GM) and dimer (170 GM), further verify these results. We demonstrate both short- (SWE) and long-wavelength excitation (LWE) fluorescence of the Soret band using 405 and 810–890 nm laser sources, respectively. Under LWE, fluorescence emission (724 nm) exhibits saturation at a peak power density of 1.5 GW/cm2. For SWE, we observe linear degradation of fluorescence for both DrBphP-PCMs, decreasing by 32% as the temperature rises from 19 to 38°C. Conversely, under LWE, the monomeric DrBphP-PCM's brightness increases up to 182% (at 37°C), surpassing the dimeric form's fluorescence rise by 39%. These findings establish the monomeric DrBphP-PCM as a promising template for developing NIR imaging and optogenetic probes operating under the determined optimal parameters for its 2P photoconversion and LWE fluorescence.

Abstract: Transcription factors relay information from the external environment to gene regulatory networks that control cell physiology. To confer signalling specificity, robustness and coordination, these signalling networks use temporal communication codes, such as the amplitude, duration or frequency of signals. Although much is known about how temporal information is encoded, a mechanistic understanding of how gene regulatory networks decode signalling dynamics is lacking. Recent advances in our understanding of phase separation of transcriptional condensates provide new biophysical frameworks for both temporal encoding and decoding mechanisms. In this Perspective, we summarize the mechanisms by which transcriptional condensates could enable temporal decoding through signal adaptation, memory and persistence. We further outline methods to probe and manipulate dynamic communication codes of transcription factors and condensates to rationally control gene activation.

Abstract: Adrenoceptors (ARs) play a vital role in various physiological processes and are key therapeutic targets. The advent of optical control techniques, including optogenetics and photopharmacology, offers the potential to modulate AR signaling with precise temporal and spatial resolution. In this review, we summarize the latest advancements in the optical control of AR signaling, encompassing optogenetics, photocaged compounds, and photoswitchable compounds. We also discuss the limitations of current tools and provide an outlook on the next generation of optogenetic and photopharmacological tools. These emerging optical technologies not only enhance our understanding of AR signaling but also pave the way for potential therapeutic developments.

Abstract: A near-infrared optogenetic system was developed for the controlled expression of therapeutics in engineered oncolytic bacteria, demonstrating significant anti-tumor efficacy in multiple tumor mouse models. This approach offers a non-invasive, customizable method for targeted solid tumor therapy and has broader applications in engineered living therapeutics.

Abstract: Bacteria-based therapies hold great promise for cancer treatment due to their selective tumor colonization and proliferation. However, clinical application is hindered by the need for safe, precise control systems to regulate local therapeutic payload expression and release. Here we developed a near-infrared (NIR) light-mediated PadC-based photoswitch (NETMAP) system based on a chimeric phytochrome-activated diguanylyl cyclase (PadC) and a cyclic diguanylate monophosphate-dependent transcriptional activator (MrkH). The NETMAP-engineered bacteria exhibited antitumor performance in mouse tumor models with different levels of immunogenicity. Specifically, in immunogenic lymphoma tumors, NIR-induced PD-L1 and CTLA-4 nanobodies enhanced the activation of adaptive immunity. In low-immunogenic tumors-including mouse-derived colon cancer models, an orthotopic human breast cancer cell line-derived xenograft model and a colorectal cancer patient-derived xenograft model-NIR-induced azurin and cytolysin A predominantly led to tumor inhibition. Our study identifies an NIR light-mediated therapeutic platform for engineered bacteria-based therapies with customizable outputs and precise dosage control.

Abstract: The binding of photoswitchable molecules to partners forms the basis of many naturally occurring light-dependent signaling pathways and various photopharmacological and optogenetic tools. A critical parameter affecting the function of these molecules is the thermal half-life of the light state. Reports in the literature indicate that, in some cases, a binding partner can significantly influence the thermal half-life, while in other cases it has no effect. Here, we present a unifying framework for quantitatively analyzing the effects of binding partners on thermal reversion rates. We focus on photoswitchable protein/binder interactions involving LOV domains, photoactive yellow protein, and CBCR GAF domains with partners that bind either the light or the dark state of the photoswitchable domain. We show that the effect of a binding partner depends on the extent to which the transition state for reversion resembles the dark state or the light state. We quantify this resemblance with a ϕswitching value, where ϕswitching = 1 if the conformation of the part of the photoswitchable molecule that interacts with the binding partner closely resembles its dark state conformation and ϕswitching = 0 if it resembles its light state. In addition to providing information on the transition state for switching, this analysis can guide the design of photoswitchable systems that retain useful thermal half-lives in practice. The analysis also provides a basis for the use of simple kinetic measurements to determine effective changes in affinity even in complex milieu.

Abstract: The RNA N6-methyladenosine (m6A) modification is a critical regulator of various biological processes, but precise and dynamic control of m6A remains a challenge. In this work, we present a red/far-red light-inducible m6A editing system that enables efficient and reversible modulation of m6A levels with minimal off-target effects. By engineering the CRISPR dCas13 protein and sgRNA with two pairs of light-inducible heterodimerizing proteins, ΔphyA/FHY1 and Bphp1/PspR2, we achieved targeted recruitment of m6A effectors. This system significantly enhances m6A writing efficiency and allows dynamic regulation of m6A deposition and removal on specific transcripts, such as SOX2 and ACTB. Notably, reversible m6A editing was achieved through cyclic modulation at a single target site, demonstrating the ability to influence mRNA expression and modulate the differentiation state of human embryonic stem cells. This optogenetic platform offers a precise, versatile tool for cyclic and reversible m6A regulation, with broad implications for understanding RNA biology and its potential applications in research and medicine.

Abstract: Optogenetics has substantially enhanced our understanding of biological processes by enabling high-precision tracking and manipulation of individual cells. It relies on photosensitive proteins to monitor and control cellular activities, thereby paving the way for significant advancements in complex system research. Photosensitive proteins play a vital role in the development of optogenetics, facilitating the establishment of cutting-edge methods. Recent breakthroughs in protein design have opened up opportunities to develop protein-based tools that can precisely manipulate and monitor cellular activities. These advancements will significantly accelerate the development and application of optogenetic tools. This article emphasizes the pivotal role of protein design in the development of optogenetic tools, offering insights into potential future directions. We begin by providing an introduction to the historical development and fundamental principles of optogenetics, followed by an exploration of the operational mechanisms of key photosensitive domains, which includes clarifying the conformational changes they undergo in response to light, such as allosteric modulation and dimerization processes. Building on this foundation, we reveal the development of protein design tools that will enable the creation of even more sophisticated optogenetic techniques.

Abstract: With the development of metabolic engineering, increasing requirements for efficient microbial biosynthesis call for establishment of multi-strain co-culture system. Dynamic regulation of population ratios is crucial for optimizing bioproduction performance. Optogenetic systems with high universality and flexibility have the potential to realize dynamic control of population proportion. In this study, we utilized an optimized chromatic acclimation sensor/regulator (CcaS/R) system and a blue light-activated YF1-FixJ-PhlF system as induction modules. A pair of orthogonal quorum sensing systems and a toxin-antitoxin system were employed as communication module and effector module, respectively. By integrating these modules, we developed a dual light-controlled co-culture system that enables dynamic regulation of population ratios. This co-culture system provides a universal toolkit for applications in metabolic engineering and synthetic biology.

Abstract: The model liverwort Marchantia polymorpha is an emerging testbed species for plant metabolic engineering but lacks well-characterized inducible promoters, which are necessary to minimize biochemical and physiological disruption when over-accumulating target products. Here, we demonstrate the functionality of the light-inducible plant-usable light-switch elements (PULSE) optogenetic system in Marchantia and exemplify its use through the light-inducible overproduction of the bioplastic poly-3-hydroxybutyrate (PHB).

Abstract: Photosynthetic cyanobacteria can be utilised in biotechnology as environmentally sustainable cell factories to convert CO2 into a diverse range of biochemicals. However, a lack of molecular tools available for precise and dynamic control of gene expression hinders metabolic engineering and contributes to low product titres. Optogenetic tools enable light-regulated control of gene expression with high tunability and reversibility. To date, their application in cyanobacteria is limited and transferability between species remains unclear. In this study, we expressed the blue light-repressible YF1/FixJ and the green/red light-responsive CcaS/CcaR systems in Synechococcus sp. PCC 7002 and characterised their performance using GFP fluorescence assays and qRT-PCR. The YF1/FixJ system of non-cyanobacterial origin showed poor performance with a maximum dynamic range of 1.5-fold despite several steps to improve this. By contrast, the CcaS/CcaR system originating from the cyanobacterium Synechocystis sp. PCC 6803 responded well to light wavelengths and intensities, with a 6-fold increased protein fluorescence output observed after 30 min of green light. Monitoring GFP transcript levels allowed us to quantify the kinetics of transcriptional activation and deactivation and to test the effect of both multiple green/red and light/dark cycles on system performance. Finally, we increased CcaS/CcaR system activity under green light through targeted genetic modifications to the pCpcG2 output promoter. This study provides a detailed characterisation of the behaviour of the CcaS/CcaR system in Synechococcus sp. PCC 7002, as well as underlining the complexity of transferring optogenetic tools across species.

Abstract: Among all photosynthetic life forms, cyanobacteria exclusively possess a water-soluble, light-sensitive carotenoprotein complex known as orange carotenoid proteins (OCPs), crucial for their photoprotective mechanisms. These protein complexes exhibit both structural and functional modularity, with distinct C-terminal (CTD) and N-terminal domains (NTD) serving as light-responsive sensor and effector regions, respectively. The majority of cyanobacterial genomes contain genes for OCP homologs and related proteins, highlighting their essential role in survival of the organism over time. Cyanobacterial photoprotection primarily involves the translocation of carotenoid entity into the NTD, leading to remarkable conformational changes in both domains and formation of metastable OCPR. Subsequently, OCPR interacts with phycobiliprotein, inducing the quenching of excitation energy and a significant reduction in PS II fluorescence yield. In dark conditions, OCPR detaches from phycobilisomes and reverts to OCPO in the presence of fluorescent recovery proteins (FRP), sustaining a continuous cycle. Research suggests that the modular structure of the OCPs, coupled with its unique light-driven dissociation and re-association capability, opens avenues for exploiting its potential as light-controlled switches, offering various biotechnological applications.