PDE6A encodes a rod-specific phosphodiesterase that catalyzes hydrolysis of cyclic guanosine monophosphate (cGMP), playing a central role in phototransduction—the conversion of photons into electrical signals in retinal photoreceptors 1. This enzyme participates in signal transmission and amplification within the visual cascade 1. Biallelic PDE6A variants cause retinitis pigmentosa type 43 (RP43), accounting for approximately 2-5% of autosomal recessive retinitis pigmentosa cases 23. Clinical studies of 57 PDE6A-RP patients revealed mild-to-moderate visual impairment in 90%, with mean best-corrected visual acuity of 0.43 logMAR and highly variable visual field preservation 4. Disease severity correlates with specific variants, with c.998+1G>A showing more severe phenotype than c.304C>A 4. Gene supplementation therapy using AAV8-PDE6A vectors restored rod vision and preserved photoreceptor morphology in preclinical canine models 3. However, a phase I/IIa human trial of subretinal AAV8.hPDE6A showed no significant visual function improvement over one year and revealed safety concerns including central retinal thinning and visual acuity decline 5, contrasting with preclinical efficacy. Alternative therapeutic approaches, such as transcriptional activation of compensatory PDE6B via CRISPR systems, demonstrated promise in rescuing photoreceptor degeneration in mouse models 6.