{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:59:22Z","timestamp":1790668762463,"version":"4.1.0"},"reference-count":116,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Autophagy preserves cellular homeostasis through lysosomal degradation, but its machinery also participates in extracellular release. This creates a pharmacological problem: changing autophagy or extracellular vesicle (EV) output can alter intracellular disposal, inflammatory signaling and communication between cells in different directions. This Review distinguishes lysosomal degradation, direct secretory autophagy and EV-associated release, with particular attention to cargo selection, tethering, fusion and the limits of route assignment. We define secretory autophagy during lysosome inhibition as a stress-dependent response and distinguish it from regulated secretion in physiological settings. Disease comparisons across cancer, neurodegeneration, inflammation and infection show why the source cell, cargo and recipient response matter for intervention. We evaluate three strategies: restoring degradation, suppressing harmful secretion and preserving or exploiting EV-linked communication. For representative interventions, we separate pharmacological tools from genetic candidate targets and pathway-level effects, and compare functional evidence, risks and translational maturity. Dynamic imaging, single-EV profiling and orthogonal perturbations offer complementary approaches to test route-specific effects. Current evidence supports preclinical opportunities, but does not establish clinical efficacy through a specifically validated secretory-autophagy\u2013EV mechanism.<\/jats:p>","DOI":"10.3389\/fphar.2026.1958455","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:50:38Z","timestamp":1790668238000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting the secretory autophagy\u2013extracellular vesicle interface: fate decisions and translational opportunities"],"prefix":"10.3389","volume":"17","author":[{"given":"Linlin","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Stomatology, The People\u2019s Hospital of Yubei District of Chongqing","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linwei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Stomatology, The People\u2019s Hospital of Yubei District of Chongqing","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijun","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Stomatology, The People\u2019s Hospital of Yubei District of Chongqing","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changfeng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Stomatology, The People\u2019s Hospital of Yubei District of Chongqing","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"108893","DOI":"10.1016\/j.isci.2024.108893","article-title":"Lysosomal stress drives the release of pathogenic \u03b1-synuclein from macrophage lineage cells via the LRRK2-Rab10 pathway","volume":"27","author":"Abe","year":"2024","journal-title":"iScience"},{"key":"B2","doi-asserted-by":"publisher","first-page":"102219","DOI":"10.1016\/j.jbc.2022.102219","article-title":"GRASP55 regulates the unconventional secretion and aggregation of mutant huntingtin","volume":"298","author":"Ahat","year":"2022","journal-title":"J. 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