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These drugs help to address some of the basic genetic defects of CFTR; however, no suitable CFTR modulators exist for 10% of people with CF (PWCF). An alternative, mutation-agnostic therapeutic approach is therefore still required. In CF airways, elevated levels of the proprotein convertase furin contribute to the dysregulation of key processes that drive disease pathogenesis. Furin plays a critical role in the proteolytic activation of the epithelial sodium channel; hyperactivity of which causes airways dehydration and loss of effective mucociliary clearance. Furin is also responsible for the processing of transforming growth factor-\u03b2, which is increased in bronchoalveolar lavage fluid from PWCF and is associated with neutrophilic inflammation and reduced pulmonary function. Pathogenic substrates of furin include<jats:italic>Pseudomonas<\/jats:italic>exotoxin A, a major toxic product associated with<jats:italic>Pseudomonas aeruginosa<\/jats:italic>infection and the spike glycoprotein of severe acute respiratory syndrome coronavirus 2, the causative pathogen for coronavirus disease 2019. In this review we discuss the importance of furin substrates in the progression of CF airways disease and highlight selective furin inhibition as a therapeutic strategy to provide clinical benefit to all PWCF.<\/jats:p>","DOI":"10.1183\/16000617.0256-2022","type":"journal-article","created":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T08:45:11Z","timestamp":1683103511000},"page":"220256","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Furin as a therapeutic target in cystic fibrosis airways disease"],"prefix":"10.1183","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9248-5409","authenticated-orcid":false,"given":"Lisa E.J.","family":"Douglas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8599-5198","authenticated-orcid":false,"given":"James A.","family":"Reihill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bethany M.","family":"Montgomery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1923-0610","authenticated-orcid":false,"given":"S. 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