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However, their role in rare disorders is unclear. \u03b2-propeller protein-associated neurodegeneration (BPAN), caused by\n                    <jats:italic>WDR45<\/jats:italic>\n                    mutations, shares key features with PD, including iron accumulation and dopaminergic neuron loss, but the impact of microglia and mutant\n                    <jats:italic>WDR45<\/jats:italic>\n                    in BPAN pathophysiology remains unexplored. To address this, we established the first induced pluripotent stem stell (iPSC)-derived microglia model from BPAN patients. Parallel targeted transcriptomic and secretomic profiling revealed a shift from a homeostatic microglial toward a stress-adapted and transcriptionally reprogrammed state characterized by selective remodeling of immune signaling pathways and dysregulation of autophagy and cellular stress responses. Complementary secretomic analysis identified reduced secretion of lysosomal enzymes alongside increased shedding of immune-associated surface proteins, indicating altered lysosomal trafficking and remodeling of microglial immune signaling. These findings identify a distinct microglial phenotype in BPAN and implicate microglial dysfunction as a potential contributor to disease mechanisms, highlighting new avenues for therapeutic strategies targeting neuroimmune pathways.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-55648-w","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T08:10:10Z","timestamp":1781511010000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Aberrant immunomodulatory signature in \u03b2-propeller protein-associated neurodegeneration patient iPSC-derived microglia"],"prefix":"10.1038","volume":"16","author":[{"given":"Gamze","family":"\u00d6zata","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel M.","family":"Wise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida","family":"Cardona-Alberich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naiyareen F.","family":"Mayeen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan A.","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan F.","family":"Lichtenthaler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Zecca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena F.","family":"Burbulla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"55648_CR1","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1016\/j.ajhg.2012.10.019","volume":"91","author":"TB Haack","year":"2012","unstructured":"Haack, T. 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