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Figure 8. Autophagy and the secretion of extracellular vesicles. Several mechanisms determine whether autophagosomal and endosomal cargo is degraded or released into the extracellular environment. Key regulators include mTOR, a master autophagy modulator, and tetraspanin CD63, whose knockout activates mTOR. PIKfyve kinase activity promotes phagophore expansion and EV secretion. The interaction of ATG12 and ATG3 also promotes EV secretion through ALIX recruitment. Secretory autophagy, an unconventional secretory pathway, depends on ATG5 and RAB8. Additionally, RAB27A and the inhibition of PIKfyve contribute to secretory autophagy. Created in BioRender. Ju, J. (2025) https://BioRender.com/qoefza9. mTOR: Mechanistic target of rapamycin; EV: extracellular vesicle; ATG12: autophagy-related gene 12; ALIX: ALG2-interacting protein X; SKP1: S-phase kinase-associated protein 1.