Tissue Plasminogen Activator (tPA), also known as PLAT, is a 64-69 kDa extracellular glycoprotein that belongs to the peptidase S1 family of serine proteases. The biological effects of tPA include blood clot degradation, vascular remodeling, synaptic plasticity, and neurodegeneration in the brain following trauma. Human tPA is secreted as a 530 amino acid (aa) single chain polypeptide (36-562 aa) that contains an amino-terminal fibrin-"finger"-like domain, an epidermal growth factor-like domain, two kringle domains and a C-terminal serine protease catalytic domain (1, 2). The partially active single chain tPA is cleaved between Arg310-Ile311 by Plasmin, Kallikrein/KLKB1, and Coagulation Factor X/Xa to generate the mature two-chain disulfide-linked polypeptide. This mature form of tPA is 10-fold more catalytically active than the single chain (3, 4). From aa 36-562, human tPA shares 81% and 72% identity with mouse and rat tPA, respectively.