TXNRD2 encodes thioredoxin reductase 2, a mitochondrial selenoprotein essential for redox homeostasis and cellular protection against oxidative stress 1. The enzyme maintains thioredoxin in a reduced state and controls reactive oxygen species levels within mitochondria 2. TXNRD2 functions through post-translational modifications, including CoAlation at Cys-483, which regulates its enzymatic activity and protects against ferroptosis by preventing mitochondrial lipid peroxidation 3. The protein is expressed in retinal ganglion cells and the optic nerve head 4. Genetic variants in TXNRD2 are significantly associated with primary open-angle glaucoma susceptibility, with risk alleles correlating with higher gene expression levels and more severe disease phenotypes including elevated intraocular pressure and paracentral visual field loss 45. Additionally, elevated TXNRD2 serum levels serve as predictive biomarkers for castration-resistant prostate cancer development 6. The gene has also been implicated in glucocorticoid deficiency disorders, with likely deleterious homozygous variants identified in patients with compatible phenotypes 7. These findings establish TXNRD2 as a critical regulator of mitochondrial redox balance with significant clinical implications across multiple diseases.