The RIPK3-MLKL-necroptosis axis is the canonical necroptotic signaling pathway that contributes to disease pathogenesis in acute kidney injury [4], ischemic stroke [6], ischemia‒reperfusion injury of steatotic livers [51], psoriasis [52], colitis [53], etc. However, many noncanonical mechanisms of RIPK3 and MLKL have been reported in recent years. The gene discussed is MLKL; the disease is ischemic stroke.