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Various models of exosome biogenesis have been proposed. The field however, lacks the robust mechanistic studies needed to obtain a molecular understanding of vesicle secretion. Learn how one lab has taken a cargo-based approach in which the team focuses on the cis-acting signals necessary and sufficient for the budding of specific proteins. Learn from Stephen J Gould why his work supports the hypothesis that the plasma membrane is a major site of exosome budding.