Opn3, also known as encephalopsin, is a member of the opsin family and a noncanonical blue-light sensing G-protein coupled receptor (GPCR) [2,3]. It has diverse light-dependent and light-independent functions in various human tissues, participating in multiple biological processes [3].

In congenital melanocytic nevus (CMN) cells, knocking down Opn3 expression inhibits the BRAFV600E/extracellular signal-regulated kinase signaling pathway, upregulates microcephaly-related transcription factors and melanogenesis-related enzymes, increasing melanin levels, indicating it negatively regulates melanogenesis [1]. In Opn3 germline knockout mice, a refractive myopia phenotype was observed, with decreased lens thickness, shallower aqueous compartment depth, and shorter axial length, suggesting its role in normal refractive development [2]. In zebrafish, Opn3 knockdown or knockout impairs embryonic angiogenesis and vascular development, and in human umbilical vein endothelial cells (HUVECs), silencing Opn3 inhibits cellular proliferation, migration, sprouting, and tube formation, while overexpression promotes these processes, revealing its positive regulation of angiogenesis through the VEGFR2-AKT pathway [4].

In conclusion, Opn3 is crucial in processes like melanogenesis, refractive development, and angiogenesis. Studies using gene knockout models in mice and zebrafish have significantly enhanced our understanding of Opn3's functions in related disease conditions such as CMN-associated melanogenesis, myopia, and angiogenesis-related diseases [1,2,4].

References:

1. Dong, Xian, Zeng, Wen, Zhang, Wei, Gu, Lingxi, Lu, Hongguang. 2022. OPN3 Regulates Melanogenesis in Human Congenital Melanocytic Nevus Cells through Functional Interaction with BRAFV600E. In The Journal of investigative dermatology, 142, 3020-3029.e5. doi:10.1016/j.jid.2022.04.022. https://pubmed.ncbi.nlm.nih.gov/35577105/

2. Linne, Courtney, Mon, Khine Yin, D'Souza, Shane, Pardue, Machelle T, Lang, Richard A. 2023. Encephalopsin (OPN3) is required for normal refractive development and the GO/GROW response to induced myopia. In Molecular vision, 29, 39-57. doi:. https://pubmed.ncbi.nlm.nih.gov/37287644/

3. Zhang, Wei, Zeng, Wen, Li, Pinhao, Qi, Shengwen, Lu, Hongguang. 2022. The effects of missense OPN3 mutations in melanocytic lesions on protein structure and light-sensitive function. In Experimental dermatology, 31, 1932-1938. doi:10.1111/exd.14666. https://pubmed.ncbi.nlm.nih.gov/36017595/

4. Luo, Huanhuan, Zhang, Wei, Zeng, Wen, Sun, Yan, Lu, Hongguang. 2025. OPN3-mediated positive regulation of angiogenesis in HUVECs through VEGFR2 interaction. In Communications biology, 8, 529. doi:10.1038/s42003-025-07958-4. https://pubmed.ncbi.nlm.nih.gov/40164822/