The long isoform L-OGA, a bifunctional enzyme that possess a glycoside hydrolase activity and a pseudo histone-acetyl transferase domain, primarily resides in the cytoplasm and the nucleus.

However, more recent work showed that S-OGA is located in mitochondria and regulates reactive oxygen production in this organelle.

However, short stretches of about 200 amino acids in OGA have homology with some proteins such as hyaluronidase, a putative acetyltransferase, eukaryotic translation elongation factor-1γ, and the 11-1 polypeptide.

In this form, a single sugar (β-N-acetylglucosamine) is added to serine and threonine residues of nuclear or cytoplasmic proteins.

Two conserved enzymes control this glycosylation of serine and threonine: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA).

However, unlike lysosomal hexosaminidases, OGA activity is the highest at neutral pH (approximately 7) and it localizes mainly to the cytosol.

OGA and OGT are synthesized from two conserved genes and are expressed throughout the human body with high levels in the brain and pancreas.

For both types of inhibitors, OGA can be selected apart from the generic lysosomal hexosaminidases by elongating the C2 substituent in their chemical structure.