A4GNT encodes alpha-1,4-N-acetylglucosaminyltransferase (α4GnT), which catalyzes the transfer of N-acetylglucosamine residues to galactose on O-glycans, particularly core 2 branched structures on gastric mucins 1. The enzyme is essential for synthesizing type III mucin with terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues, specifically produced in the stomach, duodenum, and pancreatic duct 1. Mechanistically, αGlcNAc functions as a dual-action tumor suppressor. A4gnt-knockout mice spontaneously develop gastric adenocarcinoma through hyperplasia-dysplasia-carcinoma progression without H. pylori infection, demonstrating that αGlcNAc loss triggers tumorigenesis via inflammation-associated pathways, including upregulation of inflammatory chemokines (Ccl2, Cxcl1) and growth factors (Il-11, Hgf) 1. Additionally, αGlcNAc suppresses H. pylori colonization in gastric glands 1. Clinically, reduced αGlcNAc expression on MUC6-positive gastric cancer cells significantly correlates with invasion depth, stage, venous invasion, and poor prognosis in differentiated-type adenocarcinomas 2. Loss of αGlcNAc also serves as a biomarker for malignant potential in premalignant lesions including chr3 atrophic gastritis, pyloric gland adenoma, Barrett's esophagus, and pancreatic intraductal neoplasms 3. Genetic variation in A4GNT associates with H. pylori infection susceptibility 4. These findings establish A4GNT-mediated glycosylation as critical for gastric cancer prevention and a promising therapeutic target.