GPX5 (glutathione peroxidase 5) is a selenium-independent, epididymis-specific antioxidant enzyme that protects mammalian spermatozoa from oxidative damage during maturation in the male reproductive tract 1. Unlike classical glutathione peroxidases, GPX5 lacks the active site selenocysteine residue 2, yet functions as a phospholipid hydroperoxidase 2. The enzyme is secreted into the epididymal lumen and associates with sperm membranes via epididymosomes, where it catalyzes reduction of lipid peroxides and organic hydroperoxides 23. GPX5-expressing cells demonstrate significantly increased resistance to oxidative challenge, with reduced lipid peroxidation and downstream DNA lesion formation (8-oxodG) 2. In males, GPX5 deficiency correlates with age-dependent reproductive dysfunction: GPX5 knockout mice show increased spontaneous abortion and developmental defects in offspring, attributed to accumulated oxidative DNA damage in aging sperm 4. Notably, humans express severely reduced GPX5 levels compared to other mammals 2. Recent evidence identifies GPX5 as a hub gene in Parkinson's disease pathogenesis, suggesting broader oxidative stress-related roles beyond reproduction 5. These findings establish GPX5 as a critical extracellular antioxidant defense system essential for male fertility and potentially relevant to neurodegenerative disease.