CAPN1 encodes calpain-1, a calcium-dependent cysteine protease that catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction 1. The protein functions as a non-lysosomal thiol-protease that cleaves specific targets including CTBP1 and activates caspase-7 1. CAPN1 plays crucial roles in cellular processes through protein degradation, particularly by degrading PTPN1, which leads to phosphorylation and activation of c-Met and PIK3R2 signaling pathways 2. The protein is involved in autophagy regulation and inflammatory responses, with increased expression observed in various pathological conditions 3. Loss-of-function mutations in CAPN1 cause spastic paraplegia type 76 (SPG76), an autosomal recessive hereditary spastic paraplegia characterized by lower limb spasticity, ataxia, and sometimes bulbar involvement 14. Mutant CAPN1 proteins show abnormal intracellular aggregation and reduced colocalization with tubulin compared to wild-type protein 1. Additionally, CAPN1 has been implicated in cancer progression, promoting malignant behavior and drug resistance in lung adenocarcinoma 2, and serves as a host factor targeted by coronavirus inhibitors 5. The protein's dysregulation is associated with pulmonary arterial hypertension through HIF-1α signaling 6.