N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase

N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase (AGA) is a lysosomal enzyme that catalyzes the hydrolysis of the GlcNAc-Asn bond in asparagine-linked glycoproteins (UniProt: P20933). This 346-amino acid protein plays a critical role in the catabolism of glycoproteins within the lysosomal compartment.

Mutations in AGA cause aspartylglucosaminuria (AGU; MIM 208400), a rare inborn lysosomal storage disorder characterized by accumulation of glycoasparagine and progressive intellectual disability beginning in early childhood, along with coarse facial features and connective tissue abnormalities (UniProt: P20933). The protein is central to normal lysosomal glycoprotein degradation pathways.

In Alzheimer's disease, AGA is upregulated in post-mortem human brain tissue relative to age-matched controls, with a mean log2 fold-change of +0.7974 detected across one subcellular fraction in TMT-labeled proteomics (Chaparral AD proteomics). This upregulation may reflect altered lysosomal protein metabolism or increased protein turnover in the AD brain environment, though the functional significance requires further investigation.