ADAMTS5 is an extracellular matrix-degrading metalloproteinase that cleaves chondroitin sulfate proteoglycans (CSPGs), particularly aggrecan and versican, at Glu-Xaa recognition motifs 1. Beyond cartilage homeostasis, ADAMTS5 plays critical roles in cardiac ECM remodeling and vascular physiology. In heart failure, ADAMTS5-mediated versican degradation is essential for normal cardiac function; loss of ADAMTS5 catalytic activity causes versican and hyaluronic acid accumulation, reducing integrin β1 and connexin 43 levels, ultimately impairing cardiac contractility 2. Similarly, ADAMTS5 deficiency promotes vascular calcification through versican accumulation and integrin β1/FAK pathway activation in vascular smooth muscle cells 3. In osteoarthritis pathogenesis, ADAMTS5 is a principal mediator of aggrecan loss; miR-17 suppression of ADAMTS5 contributes to OA progression, while ADAMTS5 inhibition via anti-ADAMTS5 antibodies represents a therapeutic strategy 41. Genetic studies reveal ethnicity-dependent associations: the rs2830585 polymorphism is associated with musculoskeletal degenerative disease risk in Asian populations but not Caucasians 5. These findings establish ADAMTS5 as a multifunctional protease whose dysregulation contributes to musculoskeletal, cardiac, and vascular pathologies.