Beyond Cerebral Ischemia: TRPM Channels as Universal Modulators of Ischemia-Reperfusion Injury

Ischemia/reperfusion injury (IRI) is a complex pathophysiological condition resulting from temporary loss of blood flow followed by reoxygenation. A systematic literature search was conducted in PubMed, Web of Science, and Scopus up to October 2025 to identify studies on TRPM channels in ischemia/reperfusion injury (IRI). This review delves into the mechanistic roles of transient receptor potential melastatin (TRPM) channels in IRI, highlighting their involvement in key processes such as oxidative stress, calcium overload, inflammation, endothelial dysfunction, and mitochondrial damage. The aberrant activation of TRPM channels contributes to tissue damage and cell death during IRI. We provide a comprehensive overview of the impact of specific TRPM channels on IRI across different organs, including the brain, heart, liver, and kidney. Additionally, the review examines the therapeutic potential of pharmacological inhibitors or activators targeting TRPM channels, underscoring their promise as viable strategies for mitigating IRI. Our findings advocate for continued research into TRPM channels as potential therapeutic targets, offering insights into novel treatment approaches for IRI.