In ischemia–reperfusion injury, the upregulation of RIPK1 and RIPK3 results in CypD-mediated mPTP opening, Ca2+ influx and ROS generation, and the inhibition of CypD-mediated mPTP opening could alleviate ischemic stroke-induced necroptosis [179, 180]. This evidence concerns the gene RIPK1 and ischemia.