CD47, also known as Integrin-Associated Protein (IAP) and OA3, is a 40-60 kDa variably glycosylated atypical member of the immunoglobulin superfamily (1, 2). Human CD47 is an integral membrane protein that consists of a 123 amino acid (aa) extracellular domain (ECD) with a single Ig-like domain, five membrane-spanning regions with short intervening loops, and a 34 aa C-terminal cytoplasmic tail (3). Alternate splicing of human CD47 generates additional isoforms with deletions in the cytoplasmic tail (3). Within the N-terminal ECD, human CD47 shares 63% aa sequence identity with mouse and rat CD47. A portion of the N-terminal ECD can by shed from smooth muscle cells by MMP-2-mediated proteolysis (4). The ubiquitously expressed CD47 binds to SIRP family members on macrophages, neutrophils, and T cells (5, 6). These interactions prevent macrophage-mediated clearance of healthy CD47-expressing cells and promote immune cell transmigration across the vascular endothelium (5-8). The CD47-SIRP alpha interaction is species specific, and this lack of cross-species interaction has been implicated in xenotransplantation rejection (16). CD47 associates in cis with Fas on T cells and enhances Fas‑mediated apoptosis; its ligation promotes T cell anergy and dampens Th1 immune responses (9-11). CD47 also associates in cis with Integrins alpha 4 beta 1, alpha V beta 3, alpha 2b beta 3, and alpha 2 beta 1 which can positively or negatively modulate Integrin‑mediated function (2, 12). In the vasculature, CD47 binding by Thrombospondin-1 inhibits the angiogenic and vasorelaxant effects of nitric oxide (2, 13, 14). On dendritic cells and myeloma cells, CD47 ligation by TSP-1 induces giant cell formation and osteoclast differentiation (15).