Histidine-rich glycoprotein, also known as HRG and HPRG, is a glycoprotein located in plasma and platelets and contains an unusually large amount of histidine and proline.The specific functions of HRG remain unclear, but it is known that the protein binds heme, dyes, and divalent metal ions. It inhibits rosette formation and interacts with heparin, thrombospondin, and plasminogen. Two of the protein’s effects, the inhibition of fibrinolysis, and the reduction of inhibition of coagulation indicate a potential prothrombotic effect. HPRG is evolutionarily, functionally, and structurally related to cleaved high molecular weight kininogen (HKa), an anti-angiogenic polypeptide that stimulates apoptosis of proliferating endothelial cells through binding to cell-surface tropomyosin. The antiangiogenic activity of the multidomain plasma protein HPRG is localized to its histidine-proline-rich (H/P) domain and has recently been shown to be mediated, at least partially, through binding to cell-surface tropomyosin in fibroblast growth factor-2-activated endothelial cells.