Thrombospondins (TSP) are secreted multidomain glycoproteins with many putative functions including modulating cell adhesion, proliferation, migration, and angiogenesis. At least five TSPs exist: TSP-1, -2, -3, -4, and cartilage oligomeric glycoprotein (COMP)/TSP-5. The family can be divided into two subgroups. The first, TSP-1 and -2, are homotrimeric molecules, each monomer containing an N-terminal/heparin-binding domain, a coiled-coil oligomerization domain, a von Willebrand factor-type/procollagen homology domain, three type 1 thrombospondin repeats (TSR), three EGF-like repeats, seven TSP type 3 repeats, and a C-terminal globular domain. TSP-1 and -2 are thought to mediate interactions between cells and the extracellular matrix, and as such are matricellular proteins. In contrast, TSP-3, -4, and COMP/TSP-5 are homopentamers that lack the N-terminal structure of TSP-1 and -2, but have a similar arrangement of EGF and TSP type 3 repeats, and the C-terminal domain characteristic of the TSP family.