PDE6B encodes the rod-specific catalytic subunit of cyclic GMP phosphodiesterase, an enzyme critical for visual signal transduction that hydrolyzes 3',5'-cyclic GMP in photoreceptor outer segments. This hydrolysis is essential for closing cyclic nucleotide-gated ion channels and terminating the light response, thereby enabling phototransduction and normal vision. PDE6B also participates in retinal circadian rhythm entrainment via modulation of light-induced phase-shifts. Pathogenic variants in PDE6B cause autosomal recessive retinitis pigmentosa (AR-RP), accounting for approximately 2–5% of AR-RP cases. In a Japanese cohort, the PDE6B p.(Ile535Asn) variant was found in ≥10 patients and classified as an East Asian-specific founder variant 1. In Korean populations, PDE6B mutations were the most common cause of RP in patients with symptom onset in the first decade of life 2. PDE6B mutations have also been identified in Usher syndrome and cone-rod dystrophy cohorts 3. At the population level, gnomAD v4.1 classifies PDE6B as LoF-tolerant (LOEUF=1.24); however, the gene carries 171 pathogenic+likely pathogenic ClinVar variants, demonstrating that population-level constraint is distinct from clinical pathogenicity in disease contexts. Recent gene therapy approaches show clinical promise. Prime editing targeting the PDE6B Y347X mutation restored PDE6B protein expression and protected rod cells from degeneration in preclinical models 4. AAV5-mediated PDE6B gene delivery similarly preserved photoreceptor structure and improved visual function in Pde6b knockout rats 5. CRISPR activation of Pde6b rescued photoreceptor degeneration independently of the causal mutation 6.