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Review
. 2025 Jun;94(1):587-609.
doi: 10.1146/annurev-biochem-100924-012717. Epub 2025 Mar 18.

Extracellular Vesicles and Cellular Homeostasis

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Free article
Review

Extracellular Vesicles and Cellular Homeostasis

Jordan Matthew Ngo et al. Annu Rev Biochem. 2025 Jun.
Free article

Abstract

Extracellular vesicles (EVs) are secreted, membrane-enclosed particles that have been proposed to play a broad role in intercellular communication. Most often, EVs, by analogy to enveloped viruses, are suggested to fuse to or within a target cell to deliver a soluble signaling molecule into the cytoplasm. However, significant evidence supports an alternative model in which EVs are secreted to promote homeostasis. In this model, EVs are loaded with unwanted or toxic cargo, secreted upon cellular or organismal stress, and degraded by other cells. Here, we present evidence supporting this homeostatic EV model and discuss the general inefficiency of EV cargo delivery. While the homeostatic and viral delivery models for EV function are not mutually exclusive, we propose that much of the evidence presented is hard to reconcile with a broad role for EVs in cargo transfer as a means to promote intercellular communication.

Keywords: exosomes; extracellular vesicles; homeostasis; intercellular communication; microvesicles; unconventional secretion.

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