Fibroblast activation protein alpha (FAP/seprase), encoded by the human FAP gene, is a type II transmembrane serine protease of the prolyl oligopeptidase family (which includes DPPIV/CD26, DPP8, and DPP9). It is a 97-kDa homodimeric integral membrane glycoprotein with a short N-terminal cytoplasmic tail, a single transmembrane helix, and a large extracellular catalytic domain containing an eight-bladed beta-propeller and a serine protease domain. FAP is selectively expressed on activated stromal fibroblasts (cancer-associated fibroblasts, CAFs) in over 90% of epithelial carcinomas, on granulation tissue fibroblasts in healing wounds, and in fetal mesenchymal tissues, but is nearly absent from most normal adult tissues. It exhibits both dipeptidyl peptidase activity (cleaving N-terminal Pro-X bonds in substrates such as neuropeptide Y and BNP) and unique endopeptidase/gelatinase activity (cleaving Gly-Pro bonds in denatured collagen), remodeling the extracellular matrix and modulating chemokine and growth factor activity in the tumor stroma. A soluble circulating form (antiplasmin-cleaving enzyme, APCE) also exists. Subcellularly, FAP is a plasma membrane protease on activated fibroblasts, with a soluble plasma form.