2019 Volume 31 Issue 179 Pages E33-E39
Cytosolic peptide:N-glycanase (PNGase, Ngly1) is a de-N-glycosylating enzyme that cleaves N-glycans from glycoproteins. Ngly1 is known to be involved in glycan degradation in the cytosol (non-lysosomal degradation pathway), and endoplasmic reticulum-associated degradation, which is one of the quality control systems for newly synthesized glycoproteins. In 2012, a human subject harboring mutations in the NGLY1 gene was reported (NGLY1-deficiency). Patients with NGLY1-deficiency exhibit severe systemic symptoms, such as global developmental delay, neurological/musculoskeletal deficits, and hypo/alacrima. Thus, it is obvious that Ngly1 has important physiological functions. Nevertheless, how Ngly1 functions in organisms and the precise pathological mechanisms of NGLY1-deficiency remain unclear. This review summarizes recent knowledge of the physiological function of Ngly1 derived from animal models (fly and mouse), and the functional relationship between Ngly1 and nuclear factor erythroid 2-like 1 (NEF2L1, Nrf1).