CAPN2 (calpain 2) is a calcium-regulated cysteine protease that regulates multiple cellular processes through limited proteolysis of cytoskeletal and signaling proteins. As a calcium-dependent endopeptidase, CAPN2 cleaves focal adhesion proteins including FAK and talin-1, thereby modulating cytoskeletal remodeling and cell adhesion dynamics 12. CAPN2 expression is induced during high-intensity interval training and resistance exercise, where it exhibits epigenetic and proteomic memory characteristics, remaining elevated even after extended detraining periods and contributing to faster re-adaptation during retraining 34. Beyond exercise physiology, CAPN2 plays pathological roles in several diseases. In thoracic aortic dissection, dysregulated CAPN2 disrupts endothelial focal adhesion integrity through talin-1 cleavage and integrin assembly, compromising vascular barrier function 1. In pancreatic cancer, CAPN2 downregulation suppresses tumor growth and metastasis, making it a therapeutic target regulated by the METTL16-MROH8-TBP axis 5. Conversely, in hormone-sensitive prostate cancer, CAPN2 promotes apalutamide resistance by activating protective autophagy via FOXO1-mediated ATG5 regulation 6. Additionally, CAPN2 expression is transcriptionally regulated by YAP in nasopharyngeal carcinoma progression 7, and CAPN2 participates in mechanotransduction during shear stress-induced hematopoietic stem cell aging 8.