{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T23:43:36Z","timestamp":1781739816593,"version":"3.54.5"},"reference-count":81,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":1747,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>TOLLIP (Toll-interacting protein) is an intracellular adaptor protein with diverse actions throughout the body. In a context- and cell type\u2013specific manner, TOLLIP can function as an inhibitor of inflammation and endoplasmic-reticulum stress, an activator of autophagy, or a critical regulator of intracellular vacuole trafficking. The distinct functions of this protein have been linked to innate immune responses and lung epithelial-cell apoptosis. TOLLIP genetic variants have been associated with a variety of chronic lung diseases, including idiopathic pulmonary fibrosis, asthma, and primary graft dysfunction after lung transplantation, and with infections, such as tuberculosis, Legionella pneumonia, and respiratory viruses. TOLLIP exists in a delicate homeostatic balance, with both positive and negative effects on the trajectory of pulmonary diseases. This translational review summarizes the genetic and molecular associations that link TOLLIP to the development and progression of noninfectious and infectious pulmonary diseases. We highlight current limitations of in vitro and in vivo models in assessing the role of TOLLIP in these conditions, and we describe future approaches that will enable a more nuanced exploration of the role of TOLLIP in pulmonary conditions. There has been a surge in recent research evaluating the role of this protein in human diseases, but critical mechanistic pathways require further exploration. By understanding its biologic functions in disease-specific contexts, we will be able to determine whether TOLLIP can be therapeutically modulated to treat pulmonary diseases.<\/jats:p>","DOI":"10.1165\/rcmb.2020-0470tr","type":"journal-article","created":{"date-parts":[[2020,11,24]],"date-time":"2020-11-24T21:23:38Z","timestamp":1606253018000},"page":"536-546","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":26,"title":["Toll-Interacting Protein in Pulmonary Diseases. Abiding by the Goldilocks Principle"],"prefix":"10.1093","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0000-9171","authenticated-orcid":false,"given":"Xiaoyun","family":"Li","sequence":"first","affiliation":[{"name":"Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7982-5635","authenticated-orcid":false,"given":"Gillian C.","family":"Goobie","sequence":"additional","affiliation":[{"name":"Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, and"},{"name":"Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania; and"},{"name":"Clinician Investigator Program, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0392-7202","authenticated-orcid":false,"given":"Alyssa D.","family":"Gregory","sequence":"additional","affiliation":[{"name":"Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6597-7830","authenticated-orcid":false,"given":"Daniel J.","family":"Kass","sequence":"additional","affiliation":[{"name":"Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6947-2901","authenticated-orcid":false,"given":"Yingze","family":"Zhang","sequence":"additional","affiliation":[{"name":"Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, and"},{"name":"Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,5,1]]},"reference":[{"key":"2026021100481188400_bib1","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/35014038","article-title":"Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor","volume":"2","author":"Burns","year":"2000","journal-title":"Nat Cell Biol"},{"key":"2026021100481188400_bib2","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.micinf.2011.08.018","article-title":"Tollip: a multitasking protein in innate immunity and protein trafficking","volume":"14","author":"Capelluto","year":"2012","journal-title":"Microbes 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