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As autophagy is particularly relevant for cellular homeostasis in post\u2010mitotic tissues, congenital disorders of autophagy, due to monogenic defects in key autophagy genes, share a common \u201cclinical signature\u201d including neurodevelopmental, neurodegenerative, and neuromuscular features, as well as variable abnormalities of the eyes, skin, heart, bones, immune cells, and other organ systems, depending on the expression pattern and the specific function of the defective proteins. Since the clinical and genetic resolution of <jats:italic>EPG5<\/jats:italic>\u2010related Vici syndrome, the paradigmatic congenital disorder of autophagy, the widespread use of massively parallel sequencing has resulted in the identification of a growing number of autophagy\u2010associated disease genes, encoding members of the core autophagy machinery as well as related proteins. Recently identified monogenic disorders linking selective autophagy, vesicular trafficking, and other pathways have further expanded the molecular and phenotypical spectrum of congenital disorders of autophagy as a clinical disease spectrum. Moreover, significant advances in basic research have enhanced the understanding of the underlying pathophysiology as a basis for therapy development. Here, we review (i) autophagy in the context of other intracellular trafficking pathways; (ii) the main congenital disorders of autophagy and their typical clinico\u2010pathological signatures; and (iii) the recommended primary health surveillance in monogenic disorders of autophagy based on available evidence. We further discuss recently identified molecular mechanisms that inform the current understanding of autophagy in health and disease, as well as perspectives on future therapeutic approaches.<\/jats:p>","DOI":"10.1002\/jimd.12798","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T02:39:57Z","timestamp":1729219197000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["An update on autophagy disorders"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3483-5009","authenticated-orcid":false,"given":"Hormos Salimi","family":"Dafsari","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Center for Rare Diseases, Faculty of Medicine and University Hospital Cologne University of Cologne  Cologne Germany"},{"name":"Max\u2010Planck\u2010Institute for Biology of Ageing; Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD)  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Division of Metabolic Diseases Bambino Ges\u00f9 Children's Hospital IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4119-7519","authenticated-orcid":false,"given":"Afshin","family":"Saffari","sequence":"additional","affiliation":[{"name":"Division of Child Neurology and Inherited Metabolic Diseases Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0026-4714","authenticated-orcid":false,"given":"Darius","family":"Ebrahimi\u2010Fakhari","sequence":"additional","affiliation":[{"name":"Department of Neurology and F.M. 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