GALNT2 (polypeptide N-acetylgalactosaminyltransferase 2) catalyzes the initial transfer of N-acetyl-D-galactosamine to serine or threonine residues, initiating O-linked glycosylation of diverse protein substrates 1. This post-translational modification regulates critical physiological processes including lipid metabolism, insulin sensitivity, and immune function. Mechanistically, GALNT2-dependent O-linked glycosylation modulates the function of key metabolic proteins including APOC-III, ANGPTL3, and PLTP, affecting HDL-C metabolism and lipid homeostasis 2. Recently, GALNT2 was identified as an interferon-stimulated antiviral gene that restricts respiratory virus infections through O-glycosylation of viral spike proteins, blocking virus-cell fusion and reducing COVID-19 severity 3. Additionally, GALNT2 participates in human axon guidance during neurodevelopment 4. Genetically, GALNT2 variants associate with metabolic disease risk. The rs4846914 polymorphism correlates with hypertension susceptibility 5 and insulin resistance in obese PCOS patients 6. Loss-of-function variants increase hospitalization risk following SARS-CoV-2 infection 3. Functionally, GALNT2 is implicated in atherogenic dyslipidemia, type 2 diabetes, and obesity through pleiotropic effects on insulin signaling and lipid metabolism 1. Pathogenic mutations cause congenital disorder of glycosylation 2T 7.