GPX4 and selenium deficiency: The catalytic function of selenocysteine is due to its rapid deprotonation,87 while thiol groups remain protonated at neutral pH.88 It has been shown that under selenium deficiency conditions, cysteine can replace selenocysteine in various selenoproteins.112,113 However, replacing selenocysteine by cysteine in recombinant GPx4 leads to a 1000-fold reduction in catalytic activity.114 These facts suggest that selenocysteine as the catalytic moiety is necessary to guarantee a rapid reduction of hydroperoxide by GPx4 and prevent ferroptosis.86