{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:53:13Z","timestamp":1792803193865,"version":"4.5.0"},"reference-count":59,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"51","funder":[{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","award":["222002"],"award-info":[{"award-number":["222002"]}],"id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UCLH NIHR Biomedical Research Centre"},{"name":"Aligning Science Across Parkinson","award":["ASAP 000478"],"award-info":[{"award-number":["ASAP 000478"]}],"id":[{"id":"https:\/\/ror.org\/03zj4c476","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,12,19]]},"abstract":"<jats:p>\n                    Genome-wide association studies have identified\n                    <jats:italic toggle=\"yes\">Glycoprotein Nmb<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">GPNMB<\/jats:italic>\n                    ) as a risk factor for Parkinson\u2019s disease. The risk allele increases\n                    <jats:italic toggle=\"yes\">GPNMB<\/jats:italic>\n                    transcription and GPNMB protein levels in the CSF highlighting GPMNB as a potential biomarker for Parkinson\u2019s disease. However, a lack of knowledge of GPNMB\u2019s function and mechanism of secretion has hindered an interpretation of secreted GPNMB levels. In this study, we assessed the mechanism of GPNMB secretion by macrophages, the primary cell type expressing GPNMB in the brain. We show that GPNMB is secreted in response to lysosomal stress via lysosomal exocytosis and highlight the Parkinson\u2019s disease risk factor LRRK2 as a strong modulator of GPNMB secretion.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adv1434","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T18:59:52Z","timestamp":1765997992000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":18,"title":["GPNMB is a biomarker for lysosomal dysfunction and is secreted via LRRK2-modulated lysosomal exocytosis"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9594-8272","authenticated-orcid":true,"given":"Erin C.","family":"Bogacki","sequence":"first","affiliation":[{"name":"Department of Comparative Biomedical Sciences, Royal Veterinary College, Camden, NW1 0TU, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0168-4099","authenticated-orcid":true,"given":"Gustavo Morrone","family":"Parfitt","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1268-410X","authenticated-orcid":true,"given":"Adriana","family":"Cunha","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3340-5438","authenticated-orcid":true,"given":"George","family":"Longmore","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedical Sciences, Royal Veterinary College, Camden, NW1 0TU, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selina","family":"Wray","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4537-0489","authenticated-orcid":true,"given":"Patrick A.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedical Sciences, Royal Veterinary College, Camden, NW1 0TU, UK."},{"name":"Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK."},{"name":"Aligning Science Across Parkinson\u2019s Research Network, Chevy Chase, MD 20815, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2255-7371","authenticated-orcid":true,"given":"Susanne","family":"Herbst","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedical Sciences, Royal Veterinary College, Camden, NW1 0TU, UK."},{"name":"Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK."},{"name":"Aligning Science Across Parkinson\u2019s Research Network, Chevy Chase, MD 20815, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30320-5"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","unstructured":"M. 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