KLK6 is a secreted serine protease encoded by the 15-member kallikrein gene family on chromosome 19.3-13.4 1. It exhibits trypsin-like specificity, preferring Arg at the substrate P1 position and Ser/Pro at P2, enabling degradation of extracellular matrix proteins including collagen, fibronectin, and laminin 1. KLK6 also cleaves alpha-synuclein, preventing its polymerization and suggesting involvement in synucleinopathies [UniProt]. In cancer, KLK6 functions as an oncogene promoting tumor progression through multiple mechanisms. It enhances pancreatic cancer cell invasion by cleaving secreted proteins in invasion pathways 2. KLK6 promotes global succinylation, proliferation, migration, and invasion of lung adenocarcinoma cells while fostering immunosuppressive tumor microenvironments by driving fibroblast differentiation and inhibiting CD8+ T cell infiltration 3. In bladder urothelial carcinoma, KLK6 knockdown inhibits growth, migration, and triggers apoptosis 4. In pancreatic cancer, KLK6 impairs antigen presentation and recruits immunosuppressive neutrophils, reducing responses to anti-PD-1 checkpoint blockade 5. Clinically, elevated KLK6 expression predicts poor prognosis in colorectal and lung cancers and correlates with advanced disease stage and metastases 67. KLK6 represents both a prognostic biomarker and emerging therapeutic target across multiple malignancies.