KLK14

Human tissue kallikrein 14 (KLK14) is a secreted serine protease with trypsin/chymotrypsin-like specificity, predominantly expressed in skin and endocrine tissues^[1][2]. Mechanistically, KLK14 participates in proteolytic cascades that regulate desquamation, wound healing, and intercellular signaling by activating proteinase-activated receptors (PARs) in skin fibroblasts^[2][3]. Its expression is hormonally regulated by androgens and estrogens, showing synergistic upregulation in breast and prostate cancer cell lines^[4][5]. In disease models, KLK14 overexpression is observed in prostate cancer tissues and correlates with tumor stage and Gleason score, suggesting a role in tumor progression^[1][6]. Compared with other KLK isoforms, KLK14 exhibits distinct substrate specificity and paracrine effects on IL-6, IL-8, and CXCL1 secretion from fibroblasts, highlighting its unique functional profile^[2][7]. Selective inhibition of KLK14 by proteinaceous inhibitors such as vaspin demonstrates isoform-specific regulatory control, enabling modulation of inflammatory signaling and desquamation in vitro^[7][8]. Engineered KLK inhibitors based on cyclic peptide scaffolds provide potent and selective suppression of KLK14 activity, offering tools for mechanistic studies and potential therapeutic development^[8][9]. Overall, KLK14 integrates enzymatic activity, hormonal regulation, and isoform-specific signaling, making it a relevant biomarker and experimental target in oncology and dermatology research^[10][11][12].