GUCY2F encodes a retinal guanylate cyclase responsible for cyclic GMP (cGMP) synthesis in photoreceptor rods and cones 1. As a membrane-bound receptor guanylyl cyclase, GUCY2F plays an essential role in phototransduction by mediating cGMP replenishment after light exposure, supporting normal kinetics of photoreceptor sensitivity and recovery 1. While GUCY2F and its paralog GUCY2D (GC-E) are functionally redundant in rods, targeted deletion studies reveal that GUCY2F alone has minimal impact on rod and cone physiology; however, combined deletion of both cyclases produces severe retinal degeneration resembling human Leber congenital amaurosis type 1 (LCA-1), with loss of phototransduction proteins in outer segments 2. GUCY2F may also participate in trafficking of peripheral membrane proteins to the photoreceptor outer segment membrane 2. Unlike GUCY2D, which is mutated in inherited retinal diseases including early-onset LCA and cone-rod dystrophy, disease-associated mutations have not been reported in GUCY2F 1. Somatic mutations in GUCY2F have been identified in breast, lung, and pancreatic cancers, suggesting potential involvement in tumorigenesis 3.