Platelet lipid rafts: Disease regulatory hubs and precision therapeutic targets in membrane microdomains

Lipid rafts are dynamic membrane microdomains enriched in cholesterol and sphingolipids. Platelets, with their unique anucleate nature and a high cholesterol-to-phospholipid ratio, serve as an optimal model for studying lipid raft functionality. These microdomains regulate key platelet processes-including adhesion, aggregation, phosphatidylserine exposure, and the release of inflammatory mediators-by recruiting receptors such as GPIb-IX-V and GPVI, and downstream signalling molecules like Syk and Src family kinases. Consequently, platelet lipid rafts modulate a spectrum of physiological and pathological events, from thrombosis and immune regulation to tumour metastasis. This review delineates the pathogenic roles of platelet lipid rafts in atherosclerosis, sepsis, antiphospholipid syndrome, Alzheimer's disease, and cancer, elucidating underlying mechanisms such as aberrant signal activation, procoagulant microvesicle release, and intercellular crosstalk. Furthermore, we explore emerging therapeutic strategies that target the cholesterol content, protein composition, or dynamic architecture of lipid rafts, offering novel perspectives for personalised antithrombotic regimens.