GALNT1 is a glycosyltransferase that catalyzes the initial step of O-linked oligosaccharide biosynthesis by transferring N-acetyl-D-galactosamine to serine or threonine residues on protein substrates, including mucin-derived peptides. This enzyme localizes to the Golgi apparatus and endoplasmic reticulum, where it modifies diverse protein targets. Aberrant O-glycosylation by GALNT1 is a recurrent feature in multiple cancers. In hepatocellular carcinoma, GALNT1 overexpression increases EGFR O-glycosylation and promotes cell migration and invasion; knockdown of GALNT1 suppresses these malignant traits 1. In gastric cancer, GALNT1 upregulation activates Wnt/β-catenin signaling through aberrant CD44 glycosylation, enhancing proliferation, migration, and invasion 2. In bladder cancer, GALNT1 mediates O-glycosylation of Sonic Hedgehog to sustain cancer stem cell self-renewal; intravesical delivery of GALNT1 siRNA combined with the Hedgehog inhibitor cyclopamine shows antitumor activity 3. In breast cancer metastasis, the LAMTOR5/c-Jun/c-Src axis upregulates GALNT1 to increase pathological Tn antigen accumulation on MUC1 and osteopontin 4. Notably, a large genotyping study in non-Hispanic white women found no significant association between a common GALNT1 polymorphism and ovarian cancer risk 5, underscoring population-level heterogeneity. Outside oncology, GALNT1 is essential for normal cardiac valve development and function; Galnt1-deficient mice display valve stenosis, regurgitation, and altered ejection fraction through disrupted extracellular matrix remodeling and elevated BMP/MAPK signaling 6. Recent evidence suggests GALNT1 variants associate with immunodeficiency and congenital cardiomyopathy, consistent with its developmental role.