Research progress in the role and mechanism of GALNT3 in human diseases (Review).

Protein glycosylation is a crucial post-translational modification. Polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3) is a glycosyltransferase that plays an essential role in various human diseases by modifying proteins, including fibroblast growth factor 23 and mucins. In non-tumor conditions, mutations in GALNT3 result in hyperphosphatemia in familial tumoral calcinosis, and its dysregulation has been linked to coronary artery disease. Notably, GALNT3 plays a seemingly opposing role in influenza A virus infection by potentially aiding early viral replication, and later exerting antiviral effects. In cancer, the functions of GALNT3 vary by context: it acts as a tumor suppressor in lung cancer but promotes tumor progression in colorectal and ovarian cancer. GALNT3 plays a context-dependent, dual role by exerting both tumor-suppressive and tumor-promoting functions in specific subtypes of pancreatic and breast cancers. This duality is influenced by the tissue environment, substrate specificity, and regulatory networks. Therefore, GALNT3 is emerging as a promising biomarker and therapeutic target across different pathological conditions owing to its pivotal role in disease processes.