TheEPAC-RAP1signalingpathwayhasemergedasacriticalplayerinthepathogenesisofacutelunginjury(ALI),asevereinflammatoryconditionwithhighmortalityrates.Recentstudieshavehighlightedthedualroleofthispathwayinmodulatingendothelialbarrierfunction,leukocyteadhesion,andinflammatoryresponsesduringALI.WhileEPAC1activationappearstoexertprotectiveeffectsbyenhancingendothelialintegritythroughRAP1-mediatedcelljunctionstabilization,someevidencesuggestscontext-dependentpro-inflammatoryactions.Thepathway'sinvolvementinregulatingneutrophilinfiltrationandcytokineproductionhasdrawnparticularresearchinterest,withpotentialtherapeuticimplications.CurrentinvestigationsfocusonelucidatingtheprecisemolecularmechanismsandexploringpharmacologicalmodulationofEPAC-RAP1signalingasanovelstrategyforALItreatment.ThisreviewsummarizesrecentadvancesinunderstandingthecomplexrolesofEPAC-RAP1signalinginALIpathophysiologyanddiscussesremainingchallengesintranslatingthesefindingsintoclinicalapplications.
