Abstract
Opsin 5 (OPN5), also known as neuropsin, is a violet/ultraviolet (UV) light-sensitive G protein-coupled receptor (GPCR) conserved across vertebrates. Most mammals possess a single OPN5 gene (OPN5m), whereas non-mammalian species also express OPN5L1 and OPN5L2 with distinct molecular properties. Mammalian OPN5 (OPN5m) functions as a non-visual photopigment, expressed in diverse extra-retinal tissues including the skin, testis, and brain. Recent studies reveal species-specific signaling: human OPN5m preferentially activates Gq-mediated Ca(2)⁺ signaling, mouse OPN5m couples with Gi to reduce cyclic adenosine monophosphate (cAMP), avian OPN5m engages either Gi or Gq depending on species and tissue, and amphibian/fish OPN5m homologs primarily signal through Gq pathways. These diverse signaling modes underlie a wide range of physiological functions, such as circadian photoentrainment, thermoregulation, vascular development, myopia suppression, corneal wound healing, seasonal reproduction in birds, and light-dependent hormone release in fish pituitary. As modern artificial lighting and indoor lifestyles limit violet light exposure, insufficient OPN5m activation may contribute to emerging health issues, particularly the global rise in myopia. This review provides an updated overview of the molecular diversity, expression patterns, signaling mechanisms, and physiological roles of OPN5m across species, and discusses its potential clinical relevance in the context of changing light environments.