Mouse histidine-rich glycoprotein (HPRG) is a multidomain, monomeric, secreted, 67 - 75 kDa member of the cystatin superfamily of molecules (1, 2). Its name derives from the fact that 22% of its amino acids (aa) are histidine and proline. In mouse, it is synthesized as a 525 amino acid (aa) precursor that contains an 18 aa signal sequence and a 507 aa mature region (3). Five distinct domains are recognized in the mature molecule. There are two N-terminal cystatin-like modules and one His-Pro-rich region that is flanked by two Pro-rich segments (3, 4). The His-Pro-rich region contains multiple tandem repeats with a GHHPH motif, while the N- and C-termini are linked by a disulfide bond (3, 5, 6). Mouse HPRG is only 60% aa identical to human HPRG, and 79% aa identical to rat HPRG. There are multiple ligands for HPRG. These include small molecular weight molecules (metal ions; heme), hemostatic molecules (heparan sulfate; TSP; plasminogen), and immune system components (T cells; macrophages) (1, 5). About 50% of plasma plasminogen circulates bound to HPRG. Upon immobilization to cell surface tropomyosin in a Zn⁺⁺‑dependent manner, it is converted to plasmin by tPA (7 - 9). HPRG also shows antiangiogenic activity on endothelial cells (10). Finally, it binds to cytoplasmic ligand(s) exposed during cellular necrosis, and facilitates macrophage phagocytosis (11).