Transient receptor potential melastatin 4 (TRPM4)

Transient receptor potential melastatin 4 (TRPM4) is a calcium-activated non-selective cation channel that uniquely conducts monovalent ions, such as sodium and potassium, while remaining impermeable to calcium [3, 7, 16]. It acts as a critical regulator of membrane potential; by inducing depolarization, it reduces the driving force for calcium entry through other channels, thereby indirectly modulating intracellular calcium signaling [4, 14]. TRPM4 is widely expressed across various tissues and plays essential roles in physiological processes including cardiac conduction, insulin secretion, and the immune response [11, 13]. Pathologically, mutations in TRPM4 are linked to cardiac conduction diseases like Brugada syndrome, while its over-expression in several cancers promotes tumor cell migration and proliferation [10, 11, 19]. Therapeutic targeting of TRPM4 with inhibitors is currently being explored for conditions such as ischemic stroke, cerebral edema, and various malignancies [1, 2, 13].

Other names

TRPM4BCalcium-activated non-selective cation channel 1Melastatin-4hTRPM4

TRPM4 targeted drugs primarily act as small-molecule inhibitors or blockers that bind to specific pockets within the channel structure (such as the S3-S4 helices and TRP helix region) to prevent ion conduction and membrane depolarization [1, 5, 7].