GPxs are glutathione peroxidases involved in balancing the H2O2 homeostasis in signaling cascades. GPxs have been known to catalyze the reduction of H2O2 or organic hydroperoxides to water or the corresponding alcohols, respectively, typically using glutathione (GSH) as reductant. GPx8 (probable glutathione peroxidase 8) is a 209-aa, 24 kDa protein with an N-terminal cytosolic tip, a predicted transmembrane segment and a catalytic domain located in the endoplasmic reticulum (ER) lumen. GPx8 is a CysGPxs with low glutathione peroxidase activity. A recent study identified GPx8 as a cellular substrate of the hepatitis C virus NS3-4A protease. GPx8 cleavage by NS3-4A occurs at Cys11, removing the cytosolic tip of GPx8 and was observed in different experimental systems as well as in liver biopsies from patients with chronic hepatitis C.