Because the TRPM2 channel with D1066A mutation remains functionally intact (with other intracellular agonists), D1066A KI mice mirror TRPM2 KO mice in attenuating bilirubin-induced upregulation of excitability and infarct volume, leading us to the conclusion that the binding cavity in the TRPM2 channel is indispensable for bilirubin to exert its actions in stroke. The gene discussed is TRPM2; the disease is stroke disorder.