Tissue kallikrein (KLK) (KLK)

Tissue kallikreins (KLKs) represent a family of 15 homologous secreted serine proteases (KLK1–KLK15) that play critical roles in diverse physiological processes, including blood pressure regulation, skin desquamation, and semen liquefaction (Borgono & Diamandis, 2004, Nature Reviews Cancer). These enzymes are primarily known for their ability to cleave low-molecular-weight kininogen to produce kallidin (lysyl-bradykinin), a potent vasodilator (UniProt P06870). In clinical oncology, KLKs are significant as biomarkers; most notably, KLK3 (Prostate-Specific Antigen or PSA) is the standard marker for diagnosing and monitoring prostate cancer (National Cancer Institute). Beyond diagnostics, dysregulated KLK activity is implicated in various pathologies, including inflammatory skin diseases like Netherton syndrome and several types of epithelial cancers where they promote tumor growth and metastasis (Prassas et al., 2015, Endocrine Reviews). Therapeutic targeting of tissue kallikreins involves the development of small molecule inhibitors and monoclonal antibodies designed to restore homeostatic protease activity. However, the high structural homology among the 15 family members poses a significant challenge for achieving the selectivity required to avoid off-target effects and systemic toxicity (Avgeris et al., 2012, Expert Opinion on Therapeutic Targets).

Other names

Kallikrein-related peptidaseGlandular kallikreinhK familySerine protease kallikrein

Inhibition of serine protease activity to modulate the release of bioactive peptides (such as kinins) or to prevent the degradation of extracellular matrix and signaling molecules.