GALNT6 (polypeptide N-acetylgalactosaminyltransferase 6) is a Golgi-resident enzyme that catalyzes the initial step of O-linked glycosylation by transferring N-acetylgalactosamine to serine/threonine residues on target proteins 12. GALNT6 is consistently overexpressed across multiple cancer types and promotes tumorigenesis through diverse mechanisms 3. In lung adenocarcinoma, GALNT6 promotes epithelial-mesenchymal transition and metastasis by O-glycosylating the chaperone protein GRP78, enhancing MEK1/2/ERK1/2 signaling 4. The enzyme contributes to drug resistance in hepatocellular carcinoma by modifying LAPTM5 to promote autophagy and activating cancer-associated fibroblasts through the PDGFA-PDGFRB axis 5. In pancreatic ductal adenocarcinoma, GALNT6 promotes immune evasion by glycosylating STING to block its translocation and accelerate degradation, while stabilizing PD-L1 to prevent ubiquitin-mediated degradation 6. In breast cancer, GALNT6 enhances proliferation by O-glycosylating GRP78/BiP at Thr203, facilitating sustained unfolded protein response activation 7. The enzyme also promotes stemness and drug resistance through β-catenin/MUC1-C signaling pathways 8. These findings establish GALNT6 as a critical oncogenic factor and potential therapeutic target across multiple cancer types.