Extracellular vesicles (EVs) mediate cell-to-cell communication via the transfer of biomolecules locally and systemically between organs. It has been elucidated that the specific EV cargo load is fundamental for cellular response upon EV delivery. Therefore, revealing the specific molecular machinery that functionally regulates the precise EV cargo intracellularly is of importance in understanding the role of EVs in physiology and pathophysiology and conveying therapeutic use. The purpose of

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... s review is to summarize recent findings on the general rules, as well as specific modulator motifs governing EV cargo loading. Finally, we address available information on potential therapeutic strategies to alter cargo loading.