Tissue damage, such as hepatic and renal injury, initiates hepatocyte growth factor activator (HGFAC)-mediated limited proteolytic activation of the inactive single-chain precursor form of HGF. Initially, HGFAC is produced as a precursor protein, which is activated by limited proteolysis and is neutralized by specific inhibitors known as HGF activator inhibitors, designated HAIs. HAIs belong to the Kunitz-type serine protease inhibitor family. HAIs target HGF activator and are involved in the regulation of proteolytic activation of HGF in injured tissues. Human HAI-1 transcript is expressed in various human tissues, such as adult placenta, kidney, pancreas, prostate and small intestine, and fetal kidney and lung. It translates into a 478 amino acid protein. The human HAI-2 gene maps to chromosome 19q13.1 and encodes a 252 amino acid protein, also designated human placental bikunin or kop (Kunitz domain containing protein over-expressed in pancreatic cancer). HAI-1 and HAI-2 are produced in membrane-associated forms, which are secreted as active, proteolytically truncated proteins.