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There are no effective treatments for ALI\/ARDS, partly due to an incomplete understanding of its pathogenesis across different patient subpopulations, contributing to mortality rates of 25%-40%. ALI\/ARDS is characterized by lung hypoxia, inflammatory cell infiltration, edema, and endothelial cell injury and death. Lung endothelial viability is essential for gas exchange, nutrient delivery, and immune cell migration, as well as the prevention of proteinaceous fluid accumulation. Given that lung endothelial death is a predominant feature of ALI\/ARDS, its inhibition could represent a novel therapeutic strategy. In this article, we review studies examining pulmonary endothelium death during sepsis-induced ALI\/ARDS, including studies of lung endothelium apoptosis, pyroptosis, necroptosis, and ferroptosis. We also highlight gaps in current knowledge that, if addressed, could facilitate the development of effective treatments for sepsis-induced ALI\/ARDS. Future studies of the mechanisms regulating lung endothelial death may uncover novel therapeutic targets for ALI\/ARDS. These targets could be leveraged in precision medicine approaches to treat patient subpopulations most likely to benefit from inhibiting specific forms of lung endothelial death.<\/jats:p>","DOI":"10.1165\/rcmb.2025-0443tr","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:00:49Z","timestamp":1760133649000},"page":"575-589","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":0,"title":["Regulation of endothelial cell death in inflammatory lung injury"],"prefix":"10.1093","volume":"74","author":[{"given":"Mansi","family":"Upadhyay","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine , Columbia, SC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Destini","family":"Nelson","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research 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