Serpins are a superfamily of proteins classified into 16 clades (A–P). Serpins are named for their ability to inhibit serine proteases. Some are capable of cross-class inhibition of proteases from the subtilisin, papain and caspase families. Some serpins lack protease inhibitory activity and serve other roles, such as hormone transporters, molecular chaperones or catalysts for DNA condensation. Serpin E2, also known as protease nexin-1 (PN-1), inhibits the catalytic activity of proteases such as thrombin, urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA) and plasmin.? The serpin E2-protease covalent complex binds to low-density lipoprotein receptor-related protein (LRP). As a result, it undergoes endocytosis and degradation. Seripin E2 is barely detectable in plasma, but present mainly in the extracellular matrix (ECM), in which interacts with glycosaminoglycans with a high affinity. It was first identified as glia-derived nexin (GDN) in the central nervous system (CNS). In the brain, it functions as a main physiological modulator of thrombin-mediated processes such as neurite outgrowth. Serpin E2 is secreted by many different cell types, including fibroblasts, myoblasts, vascular smooth muscle cells, monocytes, and platelets. It is up-regulated in a large number of invasive/metastatic tumors including breast, prostate, pancreatic, colorectal, oral-squamous, and testicular cancers. It is required for tumor growth and malignant progression.