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-acetylgalactosamine) to serine and threonine residues onto various proteins, thereby initiating mucin-type O-linked glycosylation in the Golgi apparatus. GalNAc-T5 (Polypeptide N-acetylgalactosaminyltransferase 5), also known as UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 5, is a 940 amino acid protein that displays enzymatic activity toward EA2 peptide substrate with weaker activity toward Muc2 or Muc 1b substrates. Its N-terminal domain is involved in substrate binding and manganese coordination, while the C-terminal domain is involved in UDP-Gal binding and catalytic reaction. EXT2 directly interacts with GalNAc-T5, suggesting that these proteins may corroborate in glycosaminoglycan synthesis.