GPX5 protects cells and enzymes from oxidative damage by catalysing the reduction of hydrogen peroxide, lipid peroxides and organic hydroperoxides, using glutathione as the reducing substrate. It is classified as EC 1.11.1.9. According to UniProt, it may form a glutathione peroxidase-like protective system against peroxide damage to sperm membrane lipids.

The GPX5 gene encodes a secreted protein that belongs to the glutathione peroxidase family. Its expression is specific to the epididymis in the mammalian male reproductive tract, and it is androgen-regulated. Alternatively spliced transcript variants have been reported for this gene. Orthologues are annotated in mouse and rat, both named Gpx5.

Unlike several other characterised glutathione peroxidases, GPX5 is not a selenoprotein: it lacks the selenocysteine residue and is therefore selenium-independent. This sets it apart from family members such as GPX4. The enzyme has been proposed to protect the membranes of spermatozoa from lipid peroxidation and/or to prevent premature acrosome reaction, which makes it a point of interest in studies of epididymal biology and sperm maturation.