Kallikrein-related peptidase 10 (KLK10)

Kallikrein-related peptidase 10 (KLK10) is a secreted serine protease and member of the kallikrein family, encoded by the KLK10 gene on chromosome 19q13.4, and originally identified as "normal epithelial cell-specific 1" (NES1)[1]. KLK10 functions as a trypsin-like protease and is characterized by a conserved catalytic triad typical of the S1 family, with a substrate specificity for cleaving after basic residues[3]. In endothelial biology, KLK10 is upregulated by stable (protective) blood flow and downregulated by disturbed (pro-atherogenic) flow. It exerts anti-inflammatory, barrier-protective, and anti-atherogenic effects by inhibiting NFκB activation and reducing endothelial expression of adhesion molecules (e.g., VCAM1, ICAM1), thereby decreasing monocyte adhesion and inflammation. In cancer, KLK10 has context-dependent roles: as a tumor suppressor in some cancers (especially breast and prostate, where its loss promotes cell proliferation) and as an oncogene in others (e.g., ovarian and pancreatic cancers, where it is overexpressed). Overexpression or recombinant KLK10 protein can inhibit endothelial inflammation and atherosclerosis in mouse models and induce apoptosis while repressing proliferation in cancer cell lines[1][2]. There are currently no approved drugs specifically targeting KLK10, but recombinant KLK10 is under experimental and preclinical investigation as a therapeutic agent, and KLK10 expression may serve as a biomarker in certain vascular or oncologic settings.

Other names

Kallikrein-10NES1 (Normal epithelial cell-specific 1)PRSSL1 (Protease serine-like 1)Breast normal epithelial cell associated serine proteaseNES1Protease serine-like 1Kallikrein 10 protein 1Kallikrein 10 protein 2Kallikrein 10 protein 3Kallikrein 10 protein 4Kallikrein 10 protein 5Kallikrein 10 protein 7Kallikrein 10 protein 8Kallikrein 10 protein 9

Protease activity: extracellular cleavage of substrates leading to anti-inflammatory effects; Downregulation of vascular cell adhesion molecule 1 (VCAM1) and intracellular adhesion molecule 1 (ICAM1) expression in endothelial cells[1]; Inhibition of NFκB activation (blocks nuclear translocation and phosphorylation of p65)[1]; Induction of tumor cell apoptosis and inhibition of proliferation via downregulation of Bcl-2 and HK-2[2]