PTK6 (protein tyrosine kinase 6) is a non-receptor intracellular tyrosine kinase that exhibits context-dependent oncogenic and tumor suppressive functions 1. In normal epithelial tissues, PTK6 is expressed in differentiated cells of the gastrointestinal tract, skin, and prostate, where it correlates with cell cycle exit and differentiation 1. The protein demonstrates flexible intracellular localization due to lack of amino-terminal myristoylation/palmitoylation 1. PTK6 phosphorylates multiple substrates including AKT, p130CAS, FAK, and HNRNPH1, promoting cell proliferation, migration, and resistance to anoikis 23. In colorectal cancer, PTK6 activates autophagy by phosphorylating HNRNPH1 at Y210, promoting liquid-liquid phase separation and NBR1 splicing regulation 3. In bladder cancer, PTK6 phosphorylates ETV4 at Y392, enhancing nuclear translocation and promoting tumor-associated neutrophil infiltration and lymphangiogenesis 4. PTK6 expression is elevated in multiple cancers including breast, prostate, and colorectal cancers, where high expression correlates with worse outcomes 56. The protein's subcellular localization is crucial for its function - nuclear PTK6 in normal prostate epithelia is lost in tumors, while cytoplasmic/membrane-associated PTK6 promotes cancer progression 2. Recent therapeutic approaches include PROTAC degraders that effectively suppress PTK6 oncogenic functions 7.