TNK2 (tyrosine kinase non-receptor 2) is a cytoplasmic non-receptor tyrosine kinase that regulates cell spreading, migration, survival, and proliferation through phosphorylation of substrates including AKT1, AR, MCF2, and WASL. The protein functions in clathrin-mediated endocytosis and EGFR trafficking by binding ubiquitin and regulating ligand-induced EGFR degradation. TNK2 operates downstream of CDC42 to mediate cell migration via BCAR1 phosphorylation and may contribute to synaptic plasticity and brain development. TNK2 has emerged as an oncogenic driver across multiple malignancies through dual mechanisms: it positively regulates pro-survival factors (AKT1, AR) while negatively regulating tumor suppressors (WWOX), conferring metastatic properties on cancer cells. In prostate cancer, TNK2 phosphorylates histone H4 at tyrosine 88 to activate androgen receptor transcription in a feedforward epigenetic circuit that sustains castration-resistant disease 1. In pancreatic cancer, TNK2 directly phosphorylates STAT5A to induce HVEM expression, suppressing CD8+ T-cell function and creating an immunosuppressive tumor microenvironment; TNK2 inhibitors (AIM100 and (R)-9b) reverse this phenotype and synergize with anti-PD-1 immunotherapy 2. In prostate cancer mitochondria, TNK2 phosphorylates ATP5F1A to sustain complex V stability and energy output; TNK2 inhibitor (R)-9b induces mitophagy-based autophagy to suppress tumor growth 3. These findings establish TNK2 as a therapeutic target in multiple cancer types.