TRPM7 is a unique target for therapeutic intervention of stroke.

Ischemic stroke is a leading cause of death and long-term disabilities. The current therapy is limited to thrombolysis and mechanical recanalization, which have limited success. A better understanding of the mechanisms underlying ischemic brain injury is therefore needed for the development of more effective interventions. Glutamate receptor-mediated Ca2+ overload and neurotoxicity have been well established for decades. However, clinical trials failed to show a satisfactory effect with the antagonists of glutamate receptors. Other glutamate-independent mechanisms, such as activation of acid-sensing ion channels and transient receptor potential melastatin 7 (TRPM7), have recently emerged as important events responsible for neuronal injury under ischemic conditions. In this review, we discuss how TRPM7 channels participate in ischemic brain injury.