In agreement with the finding from a recent study that the TRPM2 channel selectively mediates brain damage induced by reperfusion, not by ischemia (Alim et al., 2013), our recent study has revealed an exclusive role for the TRPM2 channel in sustaining the cytosolic Zn2+ concentration ([Zn2+]c) during reperfusion that is causatively associated with post-ischemia neuronal death (Ye et al., 2014), implying TRPM2-dependent rise in the [Zn2+]c is critical in driving ROS-induced neuronal death. This evidence concerns the gene TRPM2 and ischemia.