Mouse Models Reveal the Physiological Functions of Cytosolic Peptide:N-Glycanase, NGLY1

Cytosolic peptide:N-glycanase (PNGase, NGLY1) is a hydrolase that catalyzes the removal of N-glycans from misfolded glycoproteins. NGLY1 contributes to cytosolic glycan degradation (non-lysosomal degradation) and one of the protein quality control systems, endoplasmic reticulum-associated degradation. NGLY1 also is responsible for full activation of a transcription factor, nuclear factor erythroid-2 like 1 (NFE2L1). NGLY1 deficiency is caused by mutations in the human NGLY1 gene. The physiological function of NGLY1 has since attracted a great deal of attention, and researchers have made great progress in terms of its elucidation. Several of these studies have used model organisms of mice, Drosophila and Caenorhabditis elegans. The focus of the present minireview is the physiological function of NGLY1, which was revealed via analyses using mouse models, and those revelations are described here.