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(Landmark Ed)"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.31083\/fbl46961","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T09:29:27Z","timestamp":1777454967000},"source":"Crossref","is-referenced-by-count":0,"title":["Discovering the Hidden Power of NGLY1: Orchestrating Immune Cell Functions and Autoimmune Diseases"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0787-5928","authenticated-orcid":true,"given":"Christina B.","family":"Brunner","sequence":"first","affiliation":[{"name":"Department of Translational Immunology, Nikolaus-Fiebiger Center of Molecular Medicine, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5906-9395","authenticated-orcid":true,"given":"Melissa C.","family":"Schubbert","sequence":"additional","affiliation":[{"name":"Department of Translational Immunology, Nikolaus-Fiebiger Center of Molecular Medicine, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6799-9273","authenticated-orcid":true,"given":"Maximilian M.","family":"Siewert","sequence":"additional","affiliation":[{"name":"Department of Translational Immunology, Nikolaus-Fiebiger Center of Molecular Medicine, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mich\u00e8le","family":"Ohnem\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Translational Immunology, Nikolaus-Fiebiger Center of Molecular Medicine, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederic","family":"Kuwert","sequence":"additional","affiliation":[{"name":"Department of Translational Immunology, Nikolaus-Fiebiger Center of Molecular Medicine, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0366-0488","authenticated-orcid":true,"given":"Ulla I. 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