Platelet glycoprotein Ib alpha chain (GPIb alpha ), also known as CD42b, is a 145 kDa type I transmembrane member of the leucine-rich repeat (LRR) family of ligand binding proteins (1-3). Mature mouse GPIb alpha contains a 596 amino acid (aa) extracellular domain (ECD), a 21 aa transmembrane domain, and a 101 aa cytoplasmic region. The ECD of mouse GPIb alpha shares 48% and 51% aa sequence identity with human and rat GPIb alpha respectively. GPIb alpha is expressed by platelets and functions as the ligand-binding component of the platelet GPIb-IX-V complex (4). LRR2 and 4 of the extracellular domain (ECD) of GPIb alpha will trigger von Willebrand factor (vWF)-dependent adhesion of platelets to the vascular endothelium under high shear stress conditions (5, 6). Furthermore, the C-terminal anionic flanking region of the LRRs contains three tyrosine residues that are post-translationally sulfated. This modification is essential for GPIb alpha binding to vWF and Thrombin (7). The C-terminal anionic region also contains a sialomucin domain with N- and O-linked carbohydrates, and two cysteines near the membrane that allow dimerization with GP1b beta (1-6). Four additional human isoforms are generated with 1-4 repeats of aa 398-411 within the sialomucin domain of mature GPIb alpha (8). The metalloproteinase TACE/ADAM17 constitutively and inducibly cleaves GPIb alpha and releases a soluble circulating form called Glycocalicin (9, 10). GPIb alpha binding to ligands such as Thrombin, Kininogen, and Coagulation Factors XI and XII helps to initiate platelet activation and coordinate the coagulation cascade (1, 11-13). Binding to vWF or Thrombospondin in the plasma or matrix, vWF or P-Selectin on endothelial cells, or the Integrin alpha M beta 2 (MAC-1) on myeloid cells, controls responses to vascular injury (1, 14). Bernard-Soulier syndrome and platelet-type von Willebrand disease are platelet function disorders that can be caused by mutations in GPIb alpha (1, 15).