The transient potential receptor melastatin‐2 (TRPM2) channel has emerged as an important Ca²⁺ signalling mechanism in a variety of cells, contributing to cellular functions that include cytokine production, insulin release, cell motility and cell death. Its ability to respond to reactive oxygen species has made TRPM2 a potential therapeutic target for chronic inflammation, neurodegenerative diseases, and oxidative stress‐related pathologies. TRPM2 is a non‐selective, calcium (Ca²⁺)‐permeable cation channel of the melastatin‐related transient receptor potential (TRPM) ion channel subfamily. It is activated by intracellular adenosine diphosphate ribose (ADPR) through a diphosphoribose hydrolase domain in its C‐terminus and regulated through a variety of factors, including synergistic facilitation by [Ca²⁺]_i, cyclic ADPR, H₂O₂, NAADP, and negative feedback regulation by AMP and permeating protons (pH). In addition to its role mediating Ca²⁺ influx into the cells, TRPM2 can also function as a lysosomal Ca²⁺ release channel, contributing to cell death. The physiological and pathophysiological context of ROS‐mediated events makes TRPM2 a promising target for the development of therapeutic tools of inflammatory and degenerative diseases.