The cytoplasmic peptide:N-glycanase (NGLY1) - Structure, expression and cellular functions

Gene. 2016 Feb 10;577(1):1-7. doi: 10.1016/j.gene.2015.11.021. Epub 2015 Nov 30.


NGLY1/Ngly1 is a cytosolic peptide:N-glycanase, i.e. de-N-glycosylating enzyme acting on N-glycoproteins in mammals, generating free, unconjugated N-glycans and deglycosylated peptides in which the N-glycosylated asparagine residues are converted to aspartates. This enzyme is known to be involved in the quality control system for the newly synthesized glycoproteins in the endoplasmic reticulum (ER). In this system, misfolded (glyco)proteins are retrotranslocated to the cytosol, where the 26S proteasomes play a central role in degrading the proteins: a process referred to as ER-associated degradation or ERAD in short. PNGase-mediated deglycosylation is believed to facilitate the efficient degradation of some misfolded glycoproteins. Human patients harboring mutations of NGLY1 gene (NGLY1-deficiency) have recently been discovered, clearly indicating the functional importance of this enzyme. This review summarizes the current state of our knowledge on NGLY1 and its gene product in mammalian cells.

Keywords: Cytosol; ER associated degradation; Endo-beta-N-acetylglucosaminidase; Mammalian cells; NGLY1; Peptide:N-glycanase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Asparagine / genetics
  • Cytosol / metabolism
  • Endoplasmic Reticulum / metabolism
  • Endoplasmic Reticulum-Associated Degradation*
  • Glycoproteins / genetics
  • Glycoproteins / metabolism
  • Glycosylation
  • Humans
  • Mammals
  • Mutation
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase* / chemistry
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase* / genetics
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase* / metabolism
  • Peptides / metabolism
  • Polysaccharides / metabolism
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / metabolism


  • Glycoproteins
  • Peptides
  • Polysaccharides
  • Asparagine
  • Proteasome Endopeptidase Complex
  • ATP dependent 26S protease
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase