GALNT4 encodes a polypeptide N-acetylgalactosaminyltransferase that catalyzes the initial step of mucin-type O-linked glycosylation by transferring N-acetyl-D-galactosamine to serine or threonine residues on target proteins 1. The enzyme localizes to the Golgi apparatus and demonstrates substrate specificity for mucins and glycoproteins including MUC7, MUC2, MUC5AC, and SELPLG 23. GALNT4 functions through direct O-glycosylation of key signaling molecules, modifying proteins such as EGFR, PSGL-1, TNFR1, and various mucins to regulate their stability and activity 145. The enzyme plays complex roles in disease pathogenesis, acting as a tumor suppressor in hepatocellular carcinoma where its loss promotes malignant transformation 1, while conversely promoting cancer stemness in lung cancer and invasive phenotypes in pancreatic cancer 23. GALNT4 significantly contributes to cardiovascular disease by enhancing atherosclerosis through promotion of monocyte adhesion, endothelial inflammation, and foam cell formation 456, and exacerbating aortic dissection via vascular smooth muscle cell dysfunction 7. However, it demonstrates protective effects in cardiac hypertrophy by inhibiting ASK1 signaling 8. These diverse functions position GALNT4 as both a potential therapeutic target and prognostic biomarker across multiple diseases.