TRPM2

TRPM2, or transient receptor potential cation channel subfamily M member 2, is a non-selective cation channel of the TRPM subfamily within the larger TRP channel family. It forms tetrameric channels with the characteristic six transmembrane segments and a pore between segments S5 and S6. The C-terminal region contains a Nudix hydrolase–like (NUDT9-H) domain that binds ADP-ribose, a key feature distinguishing TRPM2 from many other ion channels. TRPM2 is broadly expressed, with notable presence in the brain, immune cells, pancreas, heart, and endothelium.

Activation and regulation of TRPM2 are primarily driven by intracellular ADP-ribose binding to the NUDT9-H domain. Calcium ions can act as a cofactor and amplify channel activity, and oxidative or inflammatory stress increases ADP-ribose levels, promoting channel opening. The channel conducts calcium and other cations, linking cellular redox state and calcium signaling. TRPM2 activity can be modulated by cellular factors such as pH and temperature, and is subject to pharmacological inhibition in experimental settings.

Physiological roles of TRPM2 include contributions to calcium signaling in neurons and immune cells, regulation of inflammatory responses, and involvement in cell death pathways under oxidative stress. In the brain, TRPM2 has been associated with neuronal injury during ischemia and with microglial activation. In peripheral tissues, it participates in insulin secretion from pancreatic beta cells and in endothelial and immune cell function.

Clinical relevance is an active area of research. Dysregulation of TRPM2 activity has been linked to ischemia–reperfusion injury, neurodegenerative processes associated with oxidative stress, and inflammatory diseases. Experimental models suggest that genetic or pharmacological attenuation of TRPM2 can reduce cell death and tissue damage in oxidative stress conditions, highlighting its potential as a therapeutic target.