AATK (apoptosis associated tyrosine kinase) functions as a tumor suppressor gene that regulates cell proliferation and apoptosis through multiple mechanisms. AATK acts as a serine/threonine kinase that phosphorylates TP53 at Ser366 and mediates decreased expression of key cell cycle regulators Cyclin D1 and WEE1, leading to growth suppression in a kinase-dependent manner 1. The gene plays important roles in cellular differentiation, particularly in acinar-to-ductal metaplasia in pancreatic cancer, where it initiates acinar differentiation and establishes apical-basal polarization 2. AATK is frequently silenced by promoter hypermethylation in various cancers including lung, breast, and pancreatic cancers, with methylation occurring in 40-93% of cases depending on cancer type 3. This epigenetic silencing correlates with poor patient survival across multiple cancer entities 1. AATK also regulates iron homeostasis by controlling endosome recycling; its downregulation increases transferrin uptake and intracellular iron levels, enhancing susceptibility to ferroptosis in EGFR-TKI-resistant lung cancer cells 4. Additionally, AATK contributes to compensatory β-cell mass expansion in diabetes models, where both AATK and its intronic microRNA miR-338-3p are coordinately downregulated to promote β-cell proliferation 5.