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Its ectopic expression in salivary gland epithelial cells (SGECs) is induced by type I interferon (IFN) signaling and is further amplified through Toll\u2010like receptor 7 (TLR7) activation, which is implicated in the pathogenesis of Sj\u00f6gren disease (SjD). This aberrant up\u2010regulation disrupts glandular function by promoting endolysosomal degradation of aquaporin 5 (AQP5) and sodium\u2013potassium\u2013chloride cotransporter 1, leading to impaired fluid secretion and associated clinical sequelae (eg, dry mouth). Additionally, LAMP3\u2010mediated lysosomal exocytosis of DAMPs enhances monocytic bone morphogenetic protein 6 (BMP6) production, which in turn suppresses\n                    <jats:italic>AQP5<\/jats:italic>\n                    transcription. Moreover, LAMP3 drives the extracellular vesicle\u2013mediated release of autoantigens, which further amplifies autoimmunity, and lysosome\u2010dependent cell death in SGECs contributes to tissue damage. These findings establish LAMP3 as a pivotal regulatory hinge in SjD pathogenesis, linking IFN\/TLR7 signaling, lysosomal dysfunction, and glandular hypofunction. Its central role makes it a compelling therapeutic target, with strategies including IFN and TLR7 pathway inhibitors to limit its induction, restoration of lysosomal function, BMP6 inhibition to preserve AQP5 expression, and AQP gene therapy to improve fluid secretion.\n                  <\/jats:p>","DOI":"10.1002\/art.43347","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T10:43:52Z","timestamp":1754304232000},"page":"791-800","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Investigation of Lysosome\u2010Associated Membrane Protein 3 Highlighting the Role of Lysosome in Pathophysiology and Treatment of Sj\u00f6gren Disease"],"prefix":"10.1002","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2149-7573","authenticated-orcid":false,"given":"Hiroyuki","family":"Nakamura","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Endocrinology and 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