Kallistatin (SERPINA4)

Kallistatin is an endogenous serine proteinase inhibitor encoded by the SERPINA4 gene, primarily expressed in the liver but also found in the heart, kidneys, blood vessels, and plasma[1][3]. Its principal function is to inhibit tissue kallikrein, thereby regulating vascular tone, blood pressure, angiogenesis, inflammation, oxidative stress, apoptosis, and tumor progression[2][3]. Structurally, kallistatin contains two functional domains—an active site and a heparin-binding site—that mediate its biological effects, such as promoting antioxidant proteins (eNOS, SIRT1, FoxO1, SOCS3) and blocking growth factor/cytokine signaling (e.g., VEGF, TNF-α, TGF-β, HMGB1, Wnt, EGF)[3]. Decreased kallistatin levels are observed in various disease states including cardiovascular, renal, and metabolic disorders, sepsis, cancer, and diabetic complications, supporting its utility as a biomarker[3][4]. Kallistatin therapy and gene delivery have shown protection against vascular, organ injury, and tumor progression in models, positioning it as a therapeutic target for several diseases[3].

Other names

KallistatinSERPINA4KSTPI4PI-4KALKLSTKallikrein inhibitorPeptidase inhibitor 4Serpin A4Protease inhibitor 4 (kallistatin)Serine proteinase inhibitor clade A member 4Testicular secretory protein Li 22

Inhibition of tissue kallikrein enzymatic activity Blockade of signaling pathways mediated by VEGF, TNF-α, HMGB1, TGF-β, Wnt, EGF via heparin-binding domain Stimulation of antioxidant proteins (eNOS, SIRT1, FoxO1, SOCS3)