GALNT15 (polypeptide N-acetylgalactosaminyltransferase 15) catalyzes the initial step of O-linked oligosaccharide biosynthesis by transferring N-acetyl-D-galactosamine residues to serine or threonine residues on protein substrates, with preference for Muc1a [UniProt annotation]. Though displaying weaker activity than GALNT2, GALNT15 can transfer multiple GalNAc residues to peptides and operates within the Golgi apparatus as part of protein O-linked glycosylation pathways [GO Annotations]. Beyond canonical glycosylation, GALNT15 exhibits disease-relevant regulatory functions. In adipogenesis, GALNT15 knockdown suppressed adipocyte marker genes, reduced lipid accumulation, and decreased C/EBPα and PPARγ induction in human preadipocytes, identifying it as a novel adipogenic regulator 1. GALNT15 was identified as part of a seven-gene glycosylation-related prognostic signature for gastric cancer associated with tumor-infiltrating lymphocytes 2. In ovarian cancer, GALNT15 promotes macrophage polarization through O-glycosylation of PPARγ, enhancing its nuclear translocation and fatty acid oxidation metabolism, thereby fostering an immunosuppressive tumor microenvironment and predicting poorer patient outcomes 3. Additionally, GALNT15 was downregulated in TNF-transgenic arthritis models within lymphatic smooth muscle cells 4, and genome-wide association identified it as a locus associated with melatonin secretion, linking it to circadian and neurological functions 5. These findings suggest GALNT15 extends beyond glycosylation to regulate metabolic reprogramming, immune function, and disease progression across multiple pathologies.