Cartilage Oligomeric Matrix Protein (COMP), also known as Thrombospondin-5, is a 110 kDa multidomain calcium binding protein that associates with other extracellular matrix molecules. Thrombospondin-1 and -2 constitute subgroup A and form homotrimers, whereas Thrombospondin-3, -4, and COMP constitute subgroup B and form homopentamers (1-4). Mouse COMP contains a non-collagenous coiled-coil domain, four EGF-like repeats, eight TSP type-3 repeats, and a globular TSP C-terminal domain (5). It shares 92% and 98% aa sequence identity with human and rat COMP, respectively. The coiled coil domain mediates the association of COMP into disulfide-linked homopentamers with a central hub and peripheral globular domains connected by flexible strands (6, 7). An axial pore is formed by the coiled coil assembly and binds vitamin D ₃ which is involved in bone and cartilage metabolism (8). An RGD sequence in the third TSP type-3 repeat mediates chondrocyte attachment via Integrin  alpha 5 beta 1, although when reduced and in the absence of calcium, attachment is mediated via Integrin  alpha V beta 3 (9). COMP is up-regulated in rheumatoid arthritis and osteoarthritis, hepatocellular carcinomas, chronic pancreatitis, and pancreatic carcinomas (10-12). Elevated circulating COMP levels are used as a biomarker for early onset of some skeletal disorders (10). Several mutations are associated with skeletal dysplasias, and the most common, a point mutation in the third TSP type-3 repeat, results in diminished calcium binding ability (13, 14).