RGR (retinal G protein-coupled receptor) is a membrane-bound photoisomerase expressed in retinal pigment epithelium (RPE) and Müller glia that plays a critical role in visual chr10 regeneration 1. Despite its G protein-coupled receptor classification, RGR has no known coupled G protein but functions as an alternative visual cycle photoisomerase, converting all-trans-retinal (atRAL) to 11-cis-retinal (11cRAL) under photopic conditions when the classical visual cycle is insufficient 1. This photoisomerization is essential for sustaining phototransduction in bright light conditions. Mutations in human RGR are associated with inherited retinal degeneration and age-related macular degeneration (AMD) 1. An exon-skipping splice variant, RGR-d, is a persistent component of drusen in AMD pathology 2. Studies demonstrate that abnormal RGR proteins, including RGR-d, are pathogenic, causing retinal degeneration with choriocapillaris and RPE atrophy, focal basal deposit accumulation, and fundus lesions with patchy depigmentation 2. RGR-d mislocalization in cultured cells produces significant cell growth defects 2. These findings suggest a potential link between AMD and high-frequency RGR alleles, positioning RGR mutations as clinically significant contributors to vision-threatening ocular diseases.