Discovering the Hidden Power of NGLY1: Orchestrating Immune Cell Functions and Autoimmune Diseases

Brunner C, Schubbert MC, Siewert MM, Ohnemüller M, Kuwert F, Gerling-Driessen UI, Pracht K (2026)

Publication Type: Journal article, Review article

Publication year: 2026

Journal

Book Volume: 31

Article Number: 4696

Journal Issue: 4

DOI: 10.31083/FBL46961

Abstract

The enzyme N-glycanase 1 (NGLY1) regulates autophagic processes and endoplasmic reticulum (ER)-associated proteasomal degradation by de-N-glycosylation of misfolded glycoproteins. Mutations of NGLY1 that result in a loss of protein function cause congenital disorder of deglycosylation 1 (CDDG1), also known as NGLY1 deficiency. NGLY1 deficiency is associated with severe dysregulation of mitochondria and proteasomal degradation, which primarily manifests as impairments in the nervous system. However, recent studies also linked NGLY1 function to cellular processes associated with immunity and autoimmune diseases, such as rheumatoid arthritis. NGLY1 plays a distinct role in mitochondrial homeostasis, thereby potentially regulating interferon responses, cellular stress responses and innate immunity. It also controls the stability of the programmed cell death protein-1 (PD-1) receptor on T lymphocytes and cancer cells, influencing tumor immune evasion. Importantly, NGLY1 was shown to process foreign peptides destined for presentation on major histocompatibility complex (MHC) molecules, a process that enables cytotoxic T lymphocytes to identify pathogens or mutated cells. Finally, altered levels of NGLY1 may impair B lymphocytes, especially the formation and function of antibody-secreting cells. In this review, we aim to compile findings from the last three decades and explore the connections between NGLY1-controlled processes and immune cell function. Understanding NGLY1-mediated mechanisms may provide new insights into the modulation of immune responses and the development of therapeutic strategies for immune-related disorders.

Authors with CRIS profile

Involved external institutions

Albert-Ludwigs-Universität Freiburg Germany (DE)

How to cite

APA:

Brunner, C., Schubbert, M.C., Siewert, M.M., Ohnemüller, M., Kuwert, F., Gerling-Driessen, U.I., & Pracht, K. (2026). Discovering the Hidden Power of NGLY1: Orchestrating Immune Cell Functions and Autoimmune Diseases. Frontiers in Bioscience - Landmark, 31(4). https://doi.org/10.31083/FBL46961

MLA:

Brunner, Christina, et al. "Discovering the Hidden Power of NGLY1: Orchestrating Immune Cell Functions and Autoimmune Diseases." Frontiers in Bioscience - Landmark 31.4 (2026).

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