The role and signal pathways of opsin 3 in the skin: from light perception to pathophysiological mechanisms.

Opsins are a class of classic G-protein-coupled receptor superfamily members, traditionally known to play a central role in phototransduction in the retina. Recent studies have revealed that various opsins are widely expressed in the skin, making the skin an important peripheral light-sensing organ. Among these, opsin 3 (OPN3), as one of the most abundantly expressed and functionally diverse photosensitive proteins in mammalian skin, has attracted increasing attention. This narrative review systematically outlines the expression profile of OPN3 among photoreceptors in the skin. Building on this, it provides a detailed analysis of OPN3's molecular structural characteristics, the mechanisms by which it detects light signals (particularly ultraviolet and short-wavelength visible light), and the downstream signal pathways it triggers in various skin cell types (such as keratinocytes, melanocytes and fibroblasts). These pathways include, but are not limited to, the G protein-mediated PLC-IP3/DAG-Ca2+ pathway, the cAMP-MITF pathway, and interactions with cytochrome C and the TRP ion channel; together, they regulate important physiological processes in the skin, such as pigment metabolism, immune regulation, barrier function, cell proliferation and differentiation, DNA damage repair, and circadian rhythm synchronization. Furthermore, this paper explores the role of dysregulation in the OP3 signal network in skin pathophysiology, such as its potential role in UV damage, the development of melanoma, photoaging, and inflammatory skin diseases. Finally, this paper outlines the translational prospects of OPN3 as a novel therapeutic target in the treatment of photodermatoses, skin regenerative medicine, and the development of circadian rhythm-modulating skincare products.