Protein phase transitions are gaining traction among biologists for their wide-ranging roles in biological regulation. However, achieving precise control over these phenomena in vivo remains a formidable task. Optogenetic techniques present us with a potential means to control protein phase behavior with spatiotemporal precision. This review delves into the design of optogenetic tools, particularly those aimed at manipulating protein phase transitions in complex biological systems. We begin by discussing the pivotal roles of subcellular phase transitions in physiological and pathological processes. Subsequently, we offer a thorough examination of the evolution of optogenetic tools and their applications in regulating these protein phase behaviors. Furthermore, we highlight the tailored design of optogenetic tools for controlling protein phase transitions and the construction of synthetic condensates using these innovative techniques. In the long run, the development of optogenetic tools not only holds the potential to elucidate the roles of protein phase transitions in various physiological processes but also to antagonize pathological ones to reinstate cellular homeostasis, thus bringing about novel therapeutic strategies. The integration of optogenetic techniques into the study of protein phase transitions represents a significant step forward in our understanding and manipulation of biology at the subcellular level.
Keywords: Liquid−liquid phase separation; Membraneless organelle; Optogenetics; Photoreceptor protein; Protein phase transition.