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Osmotic stress, caused by different extreme conditions, such as water loss due to evaporation in hot and dry conditions, osmotic imbalance due to hypersalinity or excessive pressure, and freeze\u2010drying, causes water\u00a0loss, which severely affects cell membranes by altering the physicochemical properties of the lipid bilayer. While the organisms employ various adaptive strategies, osmolyte\u2010mediated adaptation (OMA) plays a crucial role in maintaining membrane stability under desiccation. Osmolytes such as sugars, polyols, and amino acids function as molecular stabilizers by regulating hydration, preventing deleterious phase transitions, and modulating lipid packing. While the protective roles of osmolytes in stabilizing cellular membranes are well documented in the literature, the molecular mechanism remains less explored. This article focuses on the molecular mechanism underlying OMA of the lipid bilayer under desiccation stress. We have extensively reviewed the experimental studies on OMA in lipid membranes and highlighted molecular dynamics simulation studies, including contributions from our group. We have finally discussed the future research directions in this area and their broader applications in biotechnology and astrobiology.<\/jats:p>","DOI":"10.1002\/asia.202500590","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T04:10:13Z","timestamp":1750392613000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecular Insights into Osmolyte\u2010Mediated Adaptation of Lipid Membrane of Extremophiles"],"prefix":"10.1002","volume":"20","author":[{"given":"Nirupma","family":"Rani","sequence":"first","affiliation":[{"name":"Department of Chemistry Indian Institute of Technology  Patna Bihar 801106 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkatesh","family":"Nagaraj","sequence":"additional","affiliation":[{"name":"Department of Chemistry Indian Institute of Technology  Patna Bihar 801106 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