KLK9 (kallikrein-related peptidase 9) is a serine-type endopeptidase located on chromosome 19.3-q13.4 1 that functions as a chymotrypsin-like protease with specificity for tyrosine at the P1 cleavage position 2. The enzyme is secreted and regulated by steroid hormones, particularly estrogens and progestins, in cancer cell lines 34. KLK9 exhibits tissue-specific expression including thymus, testis, spinal cord, prostate, breast, and ovary 1. Mechanistically, KLK9 activity is enhanced by Mg2+ and Ca2+ but inhibited by Zn2+ and various protease inhibitors 2. Candidate substrates include KLK10 and midkine 2. Clinically, KLK9 demonstrates significant prognostic value in hormone-responsive cancers. In breast cancer, KLK9 expression associates with early-stage disease, smaller tumor size, and longer disease-free and overall survival, particularly in estrogen/progesterone receptor-negative subgroups 3. Similarly, in ovarian cancer, KLK9 positivity correlates with early-stage disease, low-grade tumors, and substantially longer progression-free and overall survival 4. Beyond oncology, increased urinary KLK9 excretion serves as a biomarker for hypertension-induced cardiovascular and renal damage 5. Alternative splicing generates multiple KLK9 transcripts with potential diagnostic and therapeutic applications 6.