KLK4

Kallikrein-related peptidase 4 (KLK4) is a serine protease with both intracellular and extracellular activity, implicated in prostate cancer progression^[1][2]. Mechanistically, KLK4 participates in proteolytic networks that modulate cellular adhesion, extracellular matrix remodeling, and signaling pathways relevant to tumor growth^[3][4]. Compared with related isoforms such as KLK2 and KLK3, KLK4 exhibits tissue-specific expression predominantly in the prostate and shows unique substrate specificity within the kallikrein family^[2][5]. Dysregulated KLK4 expression has been detected in seminal plasma and blood serum, confirming its role as a biomarker and potential therapeutic target in prostate cancer^[2]. Structurally, KLK4 interacts with cyclic peptide inhibitors derived from MCoTI-II, which demonstrate high potency, selectivity, and the ability to penetrate cells, enabling both experimental modulation and mechanistic study of KLK4 activity^[1][6]. These inhibitors provide chemical tools for dissecting KLK4’s role in intracellular signaling and tumor cell invasion, while also allowing comparative assessment against other KLK isoforms^[1]. In experimental models, selective inhibition of KLK4 can modulate cancer cell survival and proteolytic cascades, offering a platform for preclinical evaluation of targeted therapies^[4][7]. Collectively, KLK4’s enzymatic function, disease relevance, isoform specificity, and inhibitor accessibility establish it as a critical focus for prostate cancer research and therapeutic design^[4][1].