Nucleoredoxin-like protein 2 (NXNL2)

Nucleoredoxin-like protein 2 (NXNL2) is a human gene encoding two main protein products, due to alternative splicing: the secreted rod-derived cone viability factor 2 (RdCVF2), which is implicated in neuronal (including photoreceptor) survival, and a longer thioredoxin-related protein (RdCVF2L), which acts as a redox enzyme regulating phosphorylation of microtubule-associated protein TAU. NXNL2 is expressed predominantly in the brain and sensory tissues and is essential for the maintenance of neuronal function and cellular integrity. In vivo experiments demonstrate that deletion of Nxnl2 results in progressive neural deficits—including vision loss, cognitive impairment, and age-dependent tauopathy (aggregation of TAU)—which parallels stages of human neurodegenerative diseases such as Alzheimer’s disease. The secreted isoform supports cone viability (paralleling the homologous NXNL1/RdCVF mechanism in the retina), while the intracellular thioredoxin-related isoform prevents oxidative and metabolic stress. NXNL2 is not, however, a classical drug target; there are currently no approved drugs directly targeting it, though gene therapy approaches in animal models are under investigation.

Other names

Nucleoredoxin-like protein 2NXNL2C9orf121RdCVF2Rod-derived cone viability factor 2RDCVF2RdCVF2Lnucleoredoxin-like protein 2

Neurotrophic support for cone and neuronal survival (RdCVF2); Redox regulation via thioredoxin activity (RdCVF2L); Enzymatic regulation of TAU phosphorylation; Modulation of neuronal glucose uptake (by analogy with closely related RdCVF)