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Lipids are essential components of exosomal membranes, and it is well-known that specific lipids are enriched in exosomes compared to their parent cells. In this review we discuss current knowledge about the lipid composition of exosomes. We compare published data for different lipid classes in exosomes, and what is known about their lipid species, i.e. lipid molecules with different fatty acyl groups. Moreover, we elaborate on the hypothesis about hand-shaking between the very-long-chain sphingolipids in the outer leaflet and PS 18:0/18:1 in the inner leaflet, and we propose this to be an important mechanism in membrane biology, not only for exosomes. The similarity between the lipid composition of exosomes, HIV particles, and detergent resistant membranes, used as lipid rafts models, is also discussed. Furthermore, we summarize knowledge about the role of specific lipids and lipid metabolizing enzymes on the formation and release of exosomes. Finally, the use of exosomal lipids as biomarkers and how the lipid composition of exosomes may be of importance for researchers aiming to use exosomes as drug delivery vehicles is discussed. In conclusion, we have summarized what is presently known about lipids in exosomes and identified issues that should be taken into consideration in future studies.

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