Extracellular vesicles (EVs) in neurodevelopment: The emerging role of lipids

Lipid‑dependent mechanisms of exosome biogenesis are increasingly recognized as key regulators of neurodevelopment, shaping neuronal differentiation, synaptogenesis, glia-neuron communication, and myelination. In this review we summarize recent multi‑omic, cellular, organoid, and in vivo studies showing that extracellular vesicles (EVs) influence neurodevelopmental trajectories both by delivering trophic signals that promote neurite outgrowth and synapse formation and by modulating glia-neuron crosstalk controlling inflammation, myelination, and synaptic pruning. Alterations in lipid metabolism, including cholesterol, sphingomyelin, ceramides, phosphatidylserine, and related bioactive lipids, directly affect multivesicular body formation, intraluminal vesicle budding, and cargo selection, thereby reshaping EV lipidomes and signaling during critical windows of brain maturation. Across neurodevelopmental disorders (NDDs), convergent evidence shows that EV biogenesis, lipid composition, and cargo loading are disrupted. In this sense, we discuss translational opportunities: small‑molecule modulators of sphingolipid and cholesterol pathways, dietary and metabolic interventions, and engineered EVs enriched in pro‑neurogenic miRNAs as tractable strategies to restore EV cargo composition and intercellular signalling. Collectively, the review highlights as targeting lipid pathways that govern EV biogenesis and cargo loading offers promising avenues for biomarker discovery and therapeutic intervention across NDDs.