Transfusion-related　acute　lung　injury　(TRALI)　is　a　potentially　lethal　complication　of　blood　transfusions,　characterized　by　the　rapid　onset　of　pulmonary　edema　and　hypoxemia　within　six　hours　post-transfusion.　As　one　of　the　primary　causes　of　transfusion-related　mortality,　TRALI　carries　a　significant　mortality　rate　of　6–12%.　However,　effective　treatment　strategies　for　TRALI　are　currently　lacking,　underscoring　the　urgent　need　for　a　comprehensive　and　in-depth　understanding　of　its　pathogenesis.　This　comprehensive　review　provides　an　updated　and　detailed　analysis　of　the　current　landscape　of　TRALI,　including　its　clinical　presentation,　pathogenetic　hypotheses,　animal　models,　cellular　mechanisms,　signaling　pathways,　and　potential　therapeutic　targets.　By　highlighting　the　critical　roles　of　these　pathways　and　therapies,　this　review　offers　valuable　insights　to　inform　the　development　of　preventative　and　therapeutic　strategies　and　to　guide　future　research　efforts　aimed　at　addressing　this　life-threatening　condition.　©　2025　The　Author(s).　Advanced　Science　published　by　Wiley-VCH　GmbH.