ADAMTS15 is a zinc-dependent metalloprotease with thrombospondin motifs that functions primarily in extracellular matrix organization and skeletal muscle development. It cleaves versican (VCAN) in the pericellular matrix surrounding myoblasts, facilitating myoblast contact and fusion required for muscle development and regeneration [UniProt/NCBI]. The protein exhibits context-dependent roles in disease: it functions as a tumor suppressor in colorectal cancer, where genetic inactivation promotes tumor growth and invasion 1, and shows antiangiogenic activity in intracranial aneurysms, with the p.E133Q variant aggregating in familial cases 2. In breast carcinoma, high ADAMTS15 expression predicts prolonged relapse-free survival, with low expression combined with high ADAMTS8 conferring poor prognosis 3. ADAMTS15 serves as a prognostic biomarker in Burkitt lymphoma 4 and mediates smoking-related abdominal aortic aneurysm risk through circulating protein pathways 5. Clinically, biallelic ADAMTS15 variants cause autosomal recessive distal arthrogryposis syndrome, characterized by joint contractures and spinal stiffness, reflecting its essential role in connective tissue development 6. In rheumatoid arthritis, FTO-mediated m6A modification regulates ADAMTS15 mRNA stability, influencing joint inflammation and damage 7. These findings establish ADAMTS15 as a multifunctional protease with tissue-specific roles in development, cancer suppression, and vascular homeostasis.