CD177 is a member of the uPAR/CD59/Ly6 superfamily (1). Mature mouse CD177 is a 796 amino acid (aa) protein that contains four uPAR/Ly6 domains, while human CD177 contains only two. Within common regions, mouse CD177 shares 55% and 77% aa sequence identity with human and rat CD177, respectively. CD177 is expressed on the surface of neutrophils through a glycosylphosphatidylinositol (GPI) anchor (2-4). It is nearly absent from neutrophils from paroxysmal nocturnal hemoglobinurea patients who are deficient in the ability to synthesize GPI linkages (4, 5). It is up-regulated on granulocytes from polycythemia vera and thalassemia patients (6, 7). CD177 binds to PECAM-1 on vascular endothelial cells, an interaction which mediates neutrophil adhesion to the vascular wall and neutrophil transmigration (8). It associates in cis with the Integrin MAC-1 (CD11b/CD18) (9). CD177 also associates in cis with Proteinase 3 (PR3) and is required for cell surface PR3 expression (9-11). PR3 is normally found in intracellular vesicles, but once at the cell surface it can serve as an autoimmune target for anti-neutrophil cytoplasmic antibodies (ANCA) (12). The ANCA targeting of CD177-PR3 complexes triggers neutrophil activation and vasculitis (9, 12).