NXNL1 encodes two functionally distinct protein products essential for photoreceptor survival. The short isoform, rod-derived cone viability factor (RdCVF), is a secreted trophic factor that promotes cone photoreceptor survival by enhancing aerobic glycolysis and accelerating glucose uptake through interaction with glucose transporters 1. The long isoform, RdCVFL, is an enzymatically active thioredoxin that provides antioxidant defense by reducing oxidized cysteines in photoreceptor proteins, protecting against photooxidative stress 21. In retinitis pigmentosa, rod degeneration leads to reduced NXNL1 expression and loss of metabolic and redox signaling between rods and cones, triggering secondary cone death 3. Nxnl1-deficient mice exhibit increased rod photoreceptor sensitivity to light damage, while AAV-mediated RdCVF delivery protects against photooxidative injury 2. Combined delivery of both RdCVF and RdCVFL isoforms via single AAV vectors demonstrates superior preservation of visual function, cone density, and reduced lipid peroxidation compared to RdCVF alone in retinitis pigmentosa models 4. NXNL1 expression in retinal inner neurons is regulated by transcription factors CHX10/VSX2 5. These findings support NXNL1-based gene therapy as a gene-independent treatment strategy for inherited retinal dystrophies.