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However, disease\u2010modifying therapies targeting this pathway remain unavailable. Here, we generated induced pluripotent stem cells (iPSCs) from a PARK9 patient carrying an\n                    <jats:italic>ATP13A2<\/jats:italic>\n                    mutation and established mutation\u2010corrected isogenic control iPSCs. PARK9 iPSC\u2010derived neurons recapitulated lysosomal dysfunction\u2013associated cellular phenotypes, including impaired lysosomal acidification, reduced mature cathepsin D levels, CD63\u2010positive vesicle accumulation, LC3B\u2010positive autophagosome accumulation, cytoplasmic pSer129 \u03b1\u2010synuclein accumulation, and increased cleaved caspase\u20103 signals. These phenotypes were ameliorated in mutation\u2010corrected neurons, supporting the contribution of ATP13A2 dysfunction to these abnormalities. We then performed high\u2010content imaging\u2013based compound screening targeting LC3B\u2010positive autophagosome accumulation in PARK9 neurons. A three\u2010step workflow identified 19 candidate compounds that reduced autophagosome accumulation consistent with partial improvement of lysosome\u2010dependent downstream autophagosome processing rather than simple suppression of autophagosome formation. Among these, paroxetine, Ro 25\u20106981, amisulpride, and PK11195 showed additional, compound\u2010dependent effects on PARK9\u2010associated phenotypes, including lysosomal acidification, CD63\u2010positive vesicle accumulation, cytoplasmic pSer129 \u03b1\u2010synuclein signals, and cleaved caspase\u20103 signals. These findings establish PARK9 iPSC\u2010derived neurons as a useful model of lysosomal dysfunction\u2013associated PD pathology and provide a practical screening platform for identifying candidate compounds that modulate autophagy\u2013lysosome pathway\u2010related cellular phenotypes.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70515-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70515","type":"journal-article","created":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T08:03:01Z","timestamp":1783152181000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A\n                    <scp>PARK9 iPSC<\/scp>\n                    \u2010Derived Dopaminergic Neuron Model Enables Drug Screening Targeting Autophagy\u2010Lysosome Pathway Dysfunction in Parkinson's Disease"],"prefix":"10.1111","volume":"170","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4691-4295","authenticated-orcid":false,"given":"Kei\u2010ichi","family":"Tsukiboshi","sequence":"first","affiliation":[{"name":"Center for Genomic and Regenerative Medicine, Graduate School of Medicine Juntendo University  Tokyo Japan"},{"name":"Department of Neurology, Faculty of Medicine Juntendo University  Tokyo 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