Serine peptidase inhibitor, Kunitz type 2 (SPINT2)

Serine peptidase inhibitor, Kunitz type 2 (SPINT2) is a type I transmembrane protein characterized by two extracellular Kunitz-type domains that function as potent inhibitors of a broad range of serine proteases, including hepatocyte growth factor activator, prostasin, matriptase, and TMPRSS2[3][2][4]. It is widely expressed in epithelial tissues, where it serves as a critical regulator of proteolysis, maintaining epithelial integrity, modulating sodium absorption, and acting as a tumor suppressor[3][2]. SPINT2 inhibits proteases by forming stable enzyme-inhibitor complexes, preventing their overactivity—in particular, its inhibition of TMPRSS2 is an important factor in modulating SARS-CoV-2 entry into host epithelial cells and thus plays a role in infection biology[4]. Mutations in SPINT2 can cause syndromic congenital sodium diarrhea by impairing prostasin inhibition, and its down-regulation or loss is associated with increased cancer risk in multiple tissues[2][3][4]. No drugs are currently known to target SPINT2 directly; however, its biological functions place it at the intersection of cancer, infectious disease, and epithelial physiology research.

Other names

Kunitz-type protease inhibitor 2HAI-2Hepatocyte growth factor activator inhibitor type 2Placental bikuninHGF activator inhibitor 2Kunitz domain containing protein overexpressed in pancreatic cancerDIAR3Serine protease inhibitor, Kunitz type, 2Testicular tissue protein Li 183PBKOPHAI2Kop

Inhibits serine protease activity (especially prostasin, matriptase, TMPRSS2, HGF activator). Prevents maturation/activation of target proteases by direct binding to their catalytic domains via the Kunitz domains. Modulates proteolytic processes essential for cell signaling, migration, and viral entry.