The UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAc-T) family of enzymes are substrate-specific proteins that catalyze the transfer of GalNAc (N-acetylgalactosaminyl) to serine and threonine residues onto various proteins, thereby initiating mucin-type O-linked glycosylation in Golgi apparatus. GalNAc-TL4, also known as LGALS14 or polypeptide GalNAc transferase-like protein 4, is a 607 amino acid single-pass type II membrane protein belonging to the glycosyltransferase 2 family and GalNAc-T subfamily. Localizing to Golgi apparatus, GalNAc-TL4 utilizes manganese and calcium as cofactors and may assist with the transfer of N-acetyl-D-galactosamine to a serine or threonine residue on protein receptors. GalNAc-TL4 likely catalyzes the initial reaction in O-linked oligosaccharide biosynthesis and contains a ricin B-type lectin domain, which binds to GalNAc and contributes to glycopeptide specificity, and two conserved domains located in the glycosyltransferase region. The N-terminal domain, also known as domain A or GT1 motif, may be involved in manganese coordination and substrate binding while the C-terminal domain, also known as domain B or Gal/GalNAc-T motif, is likely involved in catalytic reaction and UDP-Gal binding. GalNAc-TL4 exists as two alternatively spliced isoforms.