Tissue kallikrein and kallikrein-related peptidases (KLKs)

Tissue kallikreins and kallikrein-related peptidases (KLKs) are a family of 15 secreted serine proteases (KLK1–KLK15) that play essential roles in diverse physiological processes through regulated proteolysis (Sotiropoulou et al., 2009) [2]. KLK1, the classical tissue kallikrein, is primarily responsible for releasing kinins from kininogens, thereby regulating blood pressure, inflammation, and pain (UniProt, 2024) [4]. Other family members are localized to specific tissues, such as KLK3 (Prostate-specific antigen) in the prostate and KLK5, KLK7, and KLK14 in the epidermis, where they manage semen liquefaction and skin desquamation, respectively (Prassas et al., 2015) [3]. Dysregulation of KLK activity is strongly linked to various pathologies, most notably cancer, where they serve as both diagnostic biomarkers and drivers of tumor progression and metastasis (Borgono & Diamandis, 2004) [1]. Therapeutic strategies include the development of specific small-molecule inhibitors and monoclonal antibodies to block aberrant activity, as well as enzyme-activated prodrugs designed to exploit the localized activity of these proteases in diseased tissues. Despite their potential, the high structural homology among KLK members poses a significant challenge for achieving target selectivity and avoiding off-target effects.

Other names

Kallikrein-related peptidaseshK1-hK15Tissue kallikrein familySerine protease family

Competitive inhibition of serine protease activity and protease-mediated prodrug activation