GALNTL6 encodes a polypeptide N-acetylgalactosaminyltransferase that catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, transferring N-acetyl-D-galactosamine residues to serine or threonine residues on protein receptors in the Golgi apparatus. Beyond its canonical glycosylation function, GALNTL6 has emerged as a pleiotropic locus associated with multiple phenotypes. A long non-coding RNA (linc-GALNTL6-4) is adipocyte-specific and co-segregates with obesity, with knockdown impairing adipogenesis and inducing lipid metabolism dysfunction and inflammation 1. The GALNTL6 rs558129 polymorphism shows robust associations with athletic phenotypes: the T allele confers 5-6% higher anaerobic power and is overrepresented in power and strength athletes compared to endurance athletes and controls 2, with meta-analysis confirming the T/T genotype as more prevalent in power athletes 3. Conversely, the C allele associates with endurance performance 4. Genetically, GALNTL6 variants link to cardiometabolic traits and sepsis-associated acute kidney injury susceptibility 5, and loss-of-function of the zebrafish ortholog galntl6 modulates Duchenne muscular dystrophy severity 6. Additionally, GALNTL6 variants predict asparaginase-associated pancreatitis risk in childhood leukemia 7, and GALNTL6 amplification associates with intermediate/high-risk papillary thyroid carcinoma 8.