GPx8 binds covalently to caspase‐4/11 via disulfide bonding between cysteine 79 of GPx8 and cysteine 118 of caspase‐4, and thus restrains caspase‐4/11 activation, while GPx8 deficiency leads to caspase‐4/11‐induced inflammation during colitis and septic shock. This evidence concerns the gene GPX8 and colitis.