{Reference Type}: Journal Article {Title}: The role of calcium-calpain pathway in hyperthermia. {Author}: Enomoto A;Fukasawa T; {Journal}: Front Mol Med {Volume}: 2 {Issue}: 0 {Year}: 2022 暂无{DOI}: 10.3389/fmmed.2022.1005258 {Abstract}: Hyperthermia is a promising anticancer treatment modality. Heat stress stimulates proteolytic machineries to regulate cellular homeostasis. Calpain, an intracellular calcium (Ca2+)-dependent cysteine protease, is a modulator that governs various cellular functions. Hyperthermia induces an increase in cytosolic Ca2+ levels and triggers calpain activation. Contrastingly, pre-exposure of cells to mild hyperthermia induces thermotolerance due to the presence of cellular homeostatic processes such as heat shock response and autophagy. Recent studies suggest that calpain is a potential key molecule that links autophagy and apoptosis. In this review, we briefly introduce the regulation of intracellular Ca2+ homeostasis, basic features of calpains with their implications in cancer, immune responses, and the roles and cross-talk of calpains in cellular protection and cell death in hyperthermia.