OPN1MW encodes the medium-wavelength (green) light-sensitive visual pigment expressed in M-cone photoreceptors of the human retina 1. As a G protein-coupled receptor, OPN1MW mediates light absorption, the first step in phototransduction, initiating electrical signals essential for color vision and high-acuity vision 2. The protein is located on the X-chromosome X Xq28 and functions through adenylate cyclase-inhibiting G protein-coupled receptor signaling 1. Pathogenic variants in OPN1MW cause X-linked cone dysfunction syndromes, including blue cone monochromacy (BCM), Bornholm eye disease, and cone dystrophy, characterized by absent or defective M- and L-cone function 34. The OPN1LW/OPN1MW gene cluster exhibits complex structure with diverse haplotypes arising from unequal recombination; some haplotypes cause exon 3-skipping during splicing, contributing to vision disorders 1. Diagnostic challenges persist because short-read sequencing is inadequate for this region, leaving many patients underdiagnosed 5. Gene augmentation therapy shows promise: AAV-mediated OPN1MW expression rescued cone structure and function in BCM mouse models, with maintained visual improvement for at least 8 months when treated early (by 2 months of age) 6. Early intervention is critical, as delayed treatment at 5-7 months showed significantly reduced therapeutic efficacy 6. These findings establish OPN1MW variants as medically actionable targets for emerging retinal gene therapies.