COMP (cartilage oligomeric matrix protein) is a pentameric extracellular matrix protein primarily found in musculoskeletal tissues that plays critical roles in cartilage structural integrity and cellular survival 1. COMP functions by binding to collagens (types II and IX) and other ECM proteins, mediating chondrocyte-matrix interactions through integrin receptors 1. The protein acts as a potent apoptosis suppressor by blocking caspase-3 activation and inducing survival proteins from the IAP family 1. COMP mutations cause pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia type 1 (MED1), resulting in disproportionate short stature, joint abnormalities, and early-onset osteoarthritis 2. These mutations interfere with calcium binding and protein conformation, leading to dominant negative effects where mutant COMP is retained in endoplasmic reticulum cisternae along with type IX collagen, impairing chondrocyte function and causing premature cell death 1. Serum COMP levels are significantly reduced in PSACH patients compared to healthy controls, serving as a potential biomarker 2. COMP degradation by ADAMTS7 promotes osteogenic differentiation through BMP2 signaling, and reduced ADAMTS7-mediated COMP cleavage contributes to osteosarcoma pathogenesis 3. Additionally, COMP shows oncogenic potential through coexpression with EMT markers and association with poor survival in colon cancer 4.