NGLY1 as an Emerging Critical Modulator for Neurodevelopment and Pathogenesis in the Brain

N-glycanase 1 (NGLY1) is a cytoplasmic glycoenzyme that removes N-linked glycans from misfolded glycoproteins. It plays an important role in the endoplasmic reticulum-associated degradation (ERAD) pathway in mammalian cells. NGLY1 dysfunction in humans causes NGLY1 deficiency as a rare autosomal recessive disorder that is characterized by neurodevelopmental delay, hypotonia, movement disorders, seizures, and multi-system involvement. In this review, we summarize recent advances in understanding the neural functions of NGLY1 and the neuropathological phenotypes associated with its deficiency.