KLK3 (kallikrein-related peptidase 3), also known as prostate-specific antigen (PSA), is a serine-type endopeptidase with multiple physiological roles. Its primary characterized function is hydrolyzing semenogelin-1, leading to liquefaction of the seminal coagulum. Beyond reproduction, KLK3 exhibits proteolytic activity that activates vascular endothelial growth factors; specifically, KLK3 cleaves VEGF-C and VEGF-D at novel N-terminal sites, though the angiogenic consequences remain debated—evidence suggests KLK3 may both inhibit and promote angiogenic processes 1. Recent findings indicate KLK3 may regulate skin homeostasis through its serine protease activity 2. Clinically, KLK3 holds significant relevance as a prostate cancer biomarker. Multiple KLK3 gene polymorphisms associate with prostate cancer risk and severity; specifically, minor alleles of rs1058205, rs2735839, rs174776, and rs17632542 show significant associations with cancer development and Gleason score 3. KLK3 expression is elevated in prostate cancer tissues compared to adjacent normal tissue and correlates positively with clinical stage, Gleason grade, and lymph node metastasis 4. However, KLK3 gene deletions lead to reduced serum PSA concentrations, potentially causing false-negative screening results and compromising cancer detection 5. These findings establish KLK3 as both a functionally important protease and a clinically valuable yet complex cancer biomarker requiring careful interpretation.