RDH12 encodes an NADPH-dependent retinal dehydrogenase/reductase expressed in photoreceptor inner segments that functions as part of the visual cycle, catalyzing the conversion of all-trans-retinal back to 11-cis-retinal required for photopigment regeneration. The enzyme displays high activity toward 9-cis, 11-cis, and all-trans-retinal, and also metabolizes lipid peroxidation products such as 4-hydroxynonenal, suggesting a role in photoreceptor detoxification. RDH12 mutations cause severe early-onset inherited retinal degeneration, predominantly manifesting as Leber congenital amaurosis (LCA) or retinitis pigmentosa 1. In affected patients, the disease presents with early macular atrophy and bone spicule pigmentation appearing in childhood, with progressive photoreceptor loss and often useful residual vision retained until adolescence 2. RDH12 accounts for approximately 7–13% of LCA cases and 7% of early-onset severe retinal dystrophy in clinical cohorts 34. In vitro studies show that pathogenic RDH12 variants result in severely reduced or absent enzyme activity 1, while recent work demonstrates that 5'UTR variants can impair RDH12 protein levels through upstream open reading frame formation 5. At the population level, gnomAD v4.1 classifies this gene as loss-of-function tolerant (LOEUF=0.86); this is distinct from clinical pathogenicity in retinal disease contexts. As photoreceptor retinoid metabolism represents a validated therapeutic target, RDH12-associated disease is a candidate for gene replacement therapy development.