Glutathione peroxidase 8 (GPX8)

Glutathione peroxidase 8 (GPX8) is a type II transmembrane protein localized to the endoplasmic reticulum (ER) and is the most recently identified member of the glutathione peroxidase family[1][2][3]. Unlike several family members that use selenocysteine for catalysis, GPX8 contains a cysteine residue at its active site and lacks strong glutathione peroxidase activity due to the absence of a glutathione-binding domain[1][2]. Instead, GPX8 is believed to participate in peroxide metabolism and protein disulfide bond formation, thereby contributing to oxidative protein folding in the ER via interaction with protein disulfide isomerases (PDI) and the ER oxidoreductase ERO1α[1][3]. GPX8 is transcriptionally regulated by hypoxia-inducible factors (such as HIF1α), enriched at mitochondria-associated membranes, and implicated in ER calcium signaling[1][2]. Functionally, GPX8 is upregulated in cancers, especially mesenchymal-like aggressive tumor cells, correlating with poor prognosis and features such as migration, invasion, and epithelial–mesenchymal transition (EMT)[1][3]. Its loss results in the suppression of cancer stemness, delayed tumor initiation, and impaired regulation of autocrine cytokines (especially interleukin-6), with subsequent effects on the JAK/STAT3 signaling pathway[1]. GPX8 also participates in immune regulation and fibrosis, and has roles in non-cancer physiology such as colitis protection and viral protein processing[1]. GPX8 expression is being explored as a diagnostic or prognostic biomarker in several cancers, particularly glioblastoma, renal, and gastric cancers[3]. Direct drug targeting of GPX8 has not yet been described, and therapeutic challenges beyond its biology have not been emphasized in the literature to date.

Other names

Probable glutathione peroxidase 8GPX8GPx-8GSHPx-8UNQ847PRO1785EPLA847putative glutathione peroxidase 8