NXNL2 encodes nucleoredoxin-like 2, a thioredoxin-family protein with dual roles in sensory neuron maintenance and cancer progression. In retinal tissue, NXNL2 encodes rod-derived cone viability factor 2 (RdCVF2), which supports cone photoreceptor survival 1. The gene is regulated by DNA methylation and CRX-responsive elements that control photoreceptor-specific expression 1. NXNL2 knockout mice exhibit accelerated cone degeneration, particularly in the ventral retina 2, though unlike its paralog NXNL1, the RdCVF2L protein does not protect against photooxidative stress 3. Beyond sensory function, NXNL2 plays a pathological role in colon cancer, where elevated expression correlates with poor survival outcomes 4. High NXNL2 promotes colon cancer cell proliferation and metastasis through AKT pathway activation, and its expression is epigenetically regulated by DNA methylation 4. Additionally, NXNL2 has emerged as a genetic determinant of hemoglobin glycation index, an emerging biomarker for diabetes complications, with variant associations identified in Hispanic populations 5, and it appears associated with neurodevelopmental pathways in gestational diabetes mellitus 6. These findings suggest NXNL2 functions contextually—supporting retinal homeostasis while paradoxically promoting oncogenic pathways in cancer.