TNK1 (tyrosine kinase non-receptor 1) is a non-receptor protein tyrosine kinase with tumor suppressor properties located on chromosome 17.1 1. Its primary function involves negative regulation of cell growth through inhibition of Ras activation 2. Mechanistically, TNK1 phosphorylates Grb2 at tyrosine residues Y277 and Y287, disrupting the Grb2-Sos1 guanine exchange factor complex and reversing Ras activation 2. TNK1 activity is regulated by MARK-mediated phosphorylation at S502, which promotes binding to 14-3-3 proteins and kinase inhibition; ubiquitin binding via its C-terminal ubiquitin-association (UBA) domain activates TNK1 3. Additionally, TNK1 associates with phospholipase C-gamma1, suggesting involvement in phospholipid signal transduction 4. Disease relevance is substantial: Tnk1-deficient mice develop spontaneous tumors at high rates (43% in null mice), including lymphomas and carcinomas 2. Patients with diffuse large B-cell lymphoma display TNK1 downregulation 2. TNK1 genotype variants (rs1554948) show associations with Alzheimer's disease, with the TNK1-A allele overrepresented in cognitively normal versus impaired subjects in older age groups 5. Clinically, TNK1 inhibitor TP-5801 demonstrates nanomolar potency against TNK1-transformed cells and suppresses tumor growth in vivo 3, suggesting therapeutic potential.