Unveiling roles of NGLY1 in cellular homeostasis and related diseases

Abstract

NGLY1, a cytoplasmic enzyme, removes N-glycans from misfolded glycoproteins during endoplasmic reticulum-associated degradation (ERAD), a critical protein quality control mechanism. ERAD coordinates with the ubiquitin-proteasome system (UPS), working synergistically to maintain cellular proteostasis and mitigate protein toxicity. Emerging evidence highlights the multifaceted roles of NGLY1 in proteostasis activity, autophagy, endoplasmic reticulum stress, and related areas, all of which are connected to numerous diseases, including neurodegenerative disorders and cancer, among others. To fully understand the function of NGLY1 in cellular homeostasis, this review comprehensively discusses recent research progress and the related molecular mechanisms of NGLY1 in cellular homeostasis and associated diseases, as well as the therapeutic approaches.