Among the additional domains found in NGLY1, the PUB (PNGase- and ubiquitin-related) domain was first identified through a bioinformatics analysis. While it was initially hypothesized that it might serve as a protein-protein interaction domain, experimental evidence supporting this hypothesis is now accumulating. On the other hand, the C-terminal PAW domain (a domain present in PNGases and other worm proteins). has now been shown to be involved in the binding of oligosaccharides to PNGase. In terms of the crystal structures of mouse Ngly1, a catalytic core domain, a C-terminal domain including PAW domain and an N-terminal domain including PUB domain. have been obtained. Regarding the function of NGLY1, it has been shown that the enzyme is involved in the ER-associated degradation (ERAD), one of the ER quality control/homeostasis systems for newly synthesized glycoproteins. The functional importance of NGLY1 in the ERAD process, however, is not clearly understood. It has also been suggested that NGLY1 is closely involved in MHC class I-mediated antigen presentation. The Ngly1-mediated (glycosylated) Asn-to-Asp deamidation constitutes, together with other reactions such as transpeptidation, unconventional post-translational modifications for antigenic peptides that are presented by MHC class I molecules. Through yeast two-hybrid screening, it has been shown that NGLY1 proteins can bind to several proteins, mostly through the N-terminal domain including the PUB domain. "In vivo" and "in vitro" interactions between NGLY1 and several ERAD-related proteins have been reported. While the importance of those protein-protein interactions to NGLY1 functions remain to be clarified, it can be assumed that such interactions may be advantageous for an efficient ERAD process. In 2012, NGLY1 deficiency, involving mutations in the "NGLY1" gene locus was first identified through an exome analysis. As of now, the clinical features of 11 patients have been reported. One cerebral visual impairment (CVI) patient also had a mutation in "NGLY1" gene. The clinical effects include neuromotor impairment, intellectual disability, and neuropathy. It has also been associated with amyotrophic lateral sclerosis and Parkinson's disease. Details of the mechanism responsible for the pathogenesis of the "NGLY1"-deficiency remains unknown, while the intracellular accumulation of "N-"GlcNAc proteins, due to the excess action of cytosolic endo-b-N-acetylglucosaminidase to misfolded glycoproteins, in "Ngly1-"deficient cells has been hypothesized as a potential cause.