KLK2

KLK2 (kallikrein-related peptidase 2) is a highly active trypsin-like serine protease of the human kallikrein family that is predominantly expressed in prostatic epithelial tissue and functions through selective cleavage of arginine-containing substrates^[1]. KLK2 participates in a proteolytic network that regulates prostate physiology by converting pro-prostate-specific antigen (pro-PSA/KLK3) into its enzymatically active form, thereby contributing to seminal fluid remodeling and reproductive function^[1][4]. Mechanistically, KLK2 is an androgen-regulated protease, and experimental studies indicate that it can enhance androgen receptor signaling through promotion of ARA70-enhanced androgen receptor transactivation, linking protease activity to transcriptional programs that support prostate cancer cell growth^[2]. In prostate cancer, KLK2 expression is elevated in tumor cells and has been associated with increased proliferation and reduced apoptosis in castration-resistant disease models, supporting its relevance as both a biological marker and functional contributor to tumor progression^[2]. KLK2 may also participate in tumor-stromal communication because KLK2 can activate protease-activated receptor-1 signaling pathways that induce mitogenic responses in prostate fibroblasts^[3]. Compared with the closely related isoform KLK3 (PSA), KLK2 shares substantial sequence homology but exhibits distinct biological functions, including activation of PSA and specific androgen-responsive regulatory characteristics^[4]. For experimental applications, the prostate-restricted expression pattern and functional involvement of KLK2 in prostate cancer have motivated the development of KLK2-targeted therapeutic strategies, including selective inhibitors and protease-activated prodrug approaches for prostate cancer research^[5].