MT1E (metallothionein 1E) is a cysteine-rich metal-binding protein encoded on chromosome 16 that serves dual roles in metal homeostasis and cancer biology. Functionally, MT1E binds heavy metals (zinc, cadmium, copper) and regulates intracellular zinc ion homeostasis through zinc binding and detoxification mechanisms 1. MT1E expression is subject to transcriptional regulation by heavy metals and glucocorticoids, with localization to both cytoplasmic and nuclear compartments. In cancer, MT1E exhibits context-dependent roles. In hepatocellular carcinoma, MT1E functions as a tumor suppressor—its downregulation correlates with promoter hypermethylation, while forced expression suppresses cell growth, induces apoptosis, and reduces metastasis 2. Conversely, in gastric cancer, E2F4-mediated autophagy targets MT1E for degradation, promoting zinc homeostasis dysregulation that facilitates cancer progression 3. MT1E expression associates with transcriptional resistance programs in HER2-positive esophagogastric cancer 4 and serves as a prognostic marker in esophageal squamous cell carcinoma 5. Beyond cancer, MT1E regulates pancreatic beta-cell function and glucose metabolism. MT1E loss in CDKAL1-mutant cells increases glycolipotoxicity sensitivity, while forced MT1E expression rescues beta-cell dysfunction through ER stress relief 6. A rare MT1E variant (p.C36Y) increases type 2 diabetes risk, with transgenic models demonstrating that variant expression promotes weight gain and glucose dysregulation 7.