FAP (fibroblast activation protein alpha) is a cell surface serine protease that functions as a key regulator of extracellular matrix remodeling and fibrosis across multiple tissues. As a post-proline cleaving endopeptidase, FAP degrades gelatin and heat-denatured collagen while exhibiting dipeptidyl peptidase activity on substrates including neuropeptide Y and substance P 12. FAP is characteristically expressed on activated fibroblasts in pathological conditions rather than normal tissues 3. In fibrotic diseases, FAP+ fibroblasts serve as the primary ECM producers; increased FAP infiltration drives intestinal fibrosis in Crohn's disease through TWIST1-dependent mechanisms 4, while FAP expression correlates with periodontal bone resorption via FAP/OLN imbalance and mTOR signaling 5. FAP also promotes liver fibrosis by activating macrophages and hepatic stellate cells toward profibrogenic phenotypes 6. Beyond fibrosis, FAP+ macrophages in adipose tissue regulate diet-induced obesity through CCL8-mediated monocyte recruitment and altered energy expenditure 7. Clinically, FAP's limited expression in normal tissues makes it an attractive therapeutic target; FAP inhibitors show promise for imaging and treating FAP-positive tumors including sarcoma and breast cancer 89, while targeting FAP reduces fibrosis burden in multiple organ systems 3.