NGLY1 deficiency is a rare inherited disorder caused by mutations in the NGLY1 gene encoding N-glycanase 1 that is a hydrolase for N-linked glycosylated proteins. 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. The cytosolic enzyme N-glycanase 1, encoded by NGLY1, catalyzes the cleavage of the β-aspartyl glycosylamine bond of N-linked glycoproteins, releasing intact N-glycans from proteins bound for degradation. 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 retro-translocated 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.