{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T01:55:55Z","timestamp":1792288555775,"version":"4.4.0"},"reference-count":129,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T00:00:00Z","timestamp":1653350400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T00:00:00Z","timestamp":1653350400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:p>The endoplasmic reticulum (ER) is an intracellular organelle that fosters the correct folding of linear polypeptides and proteins, a process tightly governed by the ER\u2010resident enzymes and chaperones. Failure to shape the proper 3\u2010dimensional architecture of proteins culminates in the accumulation of misfolded or unfolded proteins within the ER, disturbs ER homeostasis, and leads to canonically defined ER stress. Recent studies have elucidated that cellular perturbations, such as lipotoxicity, can also lead to ER stress. In response to ER stress, the unfolded protein response (UPR) is activated to reestablish ER homeostasis (\u201cadaptive UPR\u201d), or, conversely, to provoke cell death when ER stress is overwhelmed and sustained (\u201cmaladaptive UPR\u201d). It is well documented that ER stress contributes to the onset and progression of multiple hepatic pathologies including NAFLD, alcohol\u2010associated liver disease, viral hepatitis, liver ischemia, drug toxicity, and liver cancers. Here, we review key studies dealing with the emerging role of ER stress and the UPR in the pathophysiology of liver diseases from cellular, murine, and human models. Specifically, we will summarize current available knowledge on pharmacological and non\u2010pharmacological interventions that may be used to target maladaptive UPR for the treatment of nonmalignant liver diseases.<\/jats:p>","DOI":"10.1002\/hep.32562","type":"journal-article","created":{"date-parts":[[2022,5,7]],"date-time":"2022-05-07T02:29:38Z","timestamp":1651890578000},"page":"619-639","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":390,"title":["Endoplasmic reticulum stress in liver diseases"],"prefix":"10.1097","volume":"77","author":[{"given":"Amir","family":"Ajoolabady","sequence":"first","affiliation":[{"name":"Shanghai Institute of Cardiovascular Diseases, Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Kaplowitz","sequence":"additional","affiliation":[{"name":"Division of Gastrointestinal and Liver Disease, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"},{"name":"USC Research Center for Liver Disease, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Lebeaupin","sequence":"additional","affiliation":[{"name":"Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Kroemer","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, Equipe labellis\u00e9e par la Ligue contre le cancer, Universit\u00e9 de Paris, Sorbonne Universit\u00e9, Inserm U1138, Institut Universitaire de France, Paris, France"},{"name":"Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif, France"},{"name":"P\u00f4le de Biologie, H\u00f4pital Europ\u00e9en Georges Pompidou, AP\u2010HP, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randal J.","family":"Kaufman","sequence":"additional","affiliation":[{"name":"Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0882-4990","authenticated-orcid":false,"given":"Harmeet","family":"Malhi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0275-0783","authenticated-orcid":false,"given":"Jun","family":"Ren","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Cardiovascular Diseases, Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China"},{"name":"Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2022,5,24]]},"reference":[{"key":"hep32562-bib-0001-20250824","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/nature17041","article-title":"Protein misfolding in the endoplasmic reticulum as a conduit to human disease","volume":"529","year":"2016","journal-title":"Nature"},{"key":"hep32562-bib-0002-20250824","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1083\/jcb.119.5.1077","article-title":"Multiple GTP\u2010binding proteins regulate vesicular transport from the ER to Golgi membranes","volume":"119","year":"1992","journal-title":"J Cell Biol"},{"key":"hep32562-bib-0003-20250824","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1210\/endrev\/bnab006","article-title":"ER stress in cardiometabolic diseases: from molecular mechanisms to 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