GUCA1B encodes guanylate cyclase-activating protein 2 (GCAP2), a calcium-sensitive regulator of retinal guanylate cyclases. The protein stimulates guanylate cyclases GUCY2D and GUCY2F when intracellular calcium is low and inhibits them when calcium rises, a critical mechanism for recovering photoreceptor sensitivity following light exposure 1. This calcium-dependent modulation occurs through calcium binding to EF-hand domains within GCAP2 2. GUCA1B mutations cause autosomal dominant retinal dystrophies with variable phenotypic expression. A G157R mutation identified in Japanese populations associates with retinitis pigmentosa, macular degeneration, and incomplete penetrance 2, while a p.Glu155Asp variant affects the EF-hand 4 calcium-binding site 3. However, GUCA1B mutations appear to be a minor cause of retinal disease in European and North American populations 3. GUCA1B was identified as a hub gene in diabetic retinopathy pathogenesis 4 and a genetic risk factor for age-related macular degeneration with pigment epithelial detachment 5. The gene is transcriptionally regulated by Mef2d in photoreceptor cells 6, and its expression is essential for normal retinal function.