The neuroprotective role of TRPC6 was suggested to occur through activation of cAMP response element-binding protein (CREB) signaling, which is disrupted following cerebral ischemia due to degradation of TRPC6 proteins in neurons by proteolytic cleavage mediated by calpain, non-lysosomal cysteine proteases activated as a result of [Ca2+]i rise from NMDA receptor activation by elevated extracellular glutamate (Du et al., 2010). The gene discussed is TRPC6; the disease is brain ischemia.