Extracellular vesicle lipidomics for disease diagnostics and mechanism-informed discovery.

Extracellular vesicles (EVs) are cell-released nanoparticles whose lipid membranes enclose molecular cargo and contribute to vesicle stability, uptake, and biological activity. EV composition encodes and transmits biological information, reflecting cellular origin, membrane remodeling, metabolism, and disease-associated stress. This makes EV lipidomics highly relevant for diagnostics, therapeutics, mechanism-informed discovery, and emerging biotechnology. Recent advances in isolation, characterization, and lipidomics approaches are making EV lipid profiles increasingly interpretable. At the same time, low sample biomass, heterogeneity, co-isolated particles, extraction bias, and variable confidence in lipid detection, annotation, and quantification remain important design considerations. In this review, we discuss how recent EV lipidomics studies are moving beyond untargeted biomarker discovery toward mechanistic questions about membrane adaptation, cellular origin, intercellular communication, and function. We then examine applications in cancer and neurodegeneration, where recent work illustrates the biological and biotechnological potential of EV lipidomes. We argue that the next phase of EV lipidomics will require stronger integration of EV characterization, quality controls, matched biofluid comparisons, and functional assays. With rigorous analytical design, EV lipidomics is evolving into a powerful platform for mechanistic discovery, diagnostic development, and therapeutic delivery.