KLK2 (kallikrein-related peptidase 2) is a serine-type endopeptidase secreted by prostate luminal epithelium 1 that cleaves Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin, functioning in the kallikrein-kinin system alongside other proteases on chromosome 19 2. While traditionally characterized as a secreted protease, KLK2 displays unexpected cell surface expression in prostate cancer cells 3. Mechanistically, KLK2 exhibits restricted enzymatic activity at pH 8.0-8.2 (found in prostate inflammation) and is activated by sodium citrate and glycosaminoglycans 1. The protease cleaves the extracellular domain of IL-10R2, reducing its surface expression on macrophages and impairing IL-10-mediated anti-inflammatory responses 1. In cancer, KLK2 expression increases in malignancy while PSA (KLK3) decreases, with KLK2 potentially mediating tumor growth and invasion through proteolytic cascades 4. KLK2 gene variants (rs2664155, rs198977) associate with elevated serum hK2 levels and prostate cancer susceptibility 56. Clinically, KLK2 emerges as a highly prostate-specific surface target; multiple therapeutic approaches including T-cell engagers, CAR-T cells, and targeted radiotherapy demonstrate preclinical and early clinical efficacy 37, establishing KLK2 as a novel therapeutic target for advanced prostate cancer.