HRG contains two cystatin-like domains and is located in plasma and platelets. The physiological function is not yet known. It binds heme, dyes and divalent metal ions. It can inhibit rosette formation and interacts with heparin, thrombospondin, and the lysine-binding site of plasminogen. A potential prothrombotic effect of HRG is indicated by the inhibition of fibrinolysis and the reduction of inhibition of coagulation. Mutations in HRG lead to thrombophilia due to abnormal histidine-rich glycoprotein levels.