TXNDC2 (thioredoxin domain containing 2) is a testis-specific redox enzyme that plays critical roles in spermatogenesis and male fertility. Primary function: TXNDC2 regulates sperm development by facilitating disulfide bond formation and correction during fibrous sheath assembly in sperm tail morphogenesis, and maintains redox homeostasis in mature spermatozoa 1. Mechanism: The protein exhibits thioredoxin-disulfide reductase activity in the presence of NADPH and thioredoxin reductase, reducing incorrect disulfide pairings in fibrous sheath constituents and protecting sperm against age-related oxidative stress 1. Disease relevance: TXNDC2 deficiency is associated with nonobstructive azoospermia (complete absence of sperm), with homozygous deletions identified in infertile patients from consanguineous families 2. TXNDC2 expression levels correlate with severe testicular pathology, with combined analysis of TXNDC2 with protamine genes (PRM1/PRM2) achieving 96.8% sensitivity and 95.5% specificity in predicting sperm retrieval outcomes 3. Clinical significance: TXNDC2 expression is downregulated in seminomas and correlates with elevated lactate dehydrogenase levels 4, and serves as a biomarker in lymphomas and gliomas 56. Restoration of TXNDC2 expression following telmisartan treatment improved spermatogenic recovery in irradiation-damaged testes 7.