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One of the recently identified subtypes of NBIA is \u03b2\u2010propeller protein\u2010associated neurodegeneration (BPAN). BPAN is caused by <jats:italic>de novo<\/jats:italic> mutations in the <jats:italic>WDR45<\/jats:italic>\/<jats:italic>WIPI4<\/jats:italic> (WD repeat domain 45) gene. WDR45 is one of the four mammalian homologs of yeast <jats:italic>Atg18<\/jats:italic>, a regulator of autophagy. WDR45 deficiency in BPAN patients and animal models may result in defects in autophagic flux. However, how WDR45 deficiency leads to brain iron overload remains unclear. To elucidate the role of WDR45, we generated a <jats:italic>WDR45<\/jats:italic>\u2010knockout (KO) SH\u2010SY5Y neuroblastoma cell line using CRISPR\u2010Cas9\u2010mediated genome editing. Using these cells, we demonstrated that the non\u2010TF (transferrin)\u2010bound iron pathway dominantly mediated the accumulation of iron. Moreover, the loss of WDR45\u00a0led to defects in ferritinophagy, a form of autophagy that degrades the iron storage protein ferritin. We showed that impaired ferritinophagy contributes to iron accumulation in <jats:italic>WDR45<\/jats:italic>\u2010KO cells. Iron accumulation was also detected in the mitochondria, which was accompanied by impaired mitochondrial respiration, elevated reactive oxygen species, and increased cell death. Thus, our study links WDR45 to specific iron acquisition pathways and ferritinophagy.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15548-fig-0009-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p>\n<jats:bold>Cover Image for this issue:<\/jats:bold> \n<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/doi.org\/10.1111\/jnc.15388\">https:\/\/doi.org\/10.1111\/jnc.15388<\/jats:ext-link>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.15548","type":"journal-article","created":{"date-parts":[[2021,11,27]],"date-time":"2021-11-27T10:13:49Z","timestamp":1638008029000},"page":"356-375","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["A neurodegeneration gene, <i>WDR45<\/i>, links impaired ferritinophagy to iron accumulation"],"prefix":"10.1111","volume":"160","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0437-4785","authenticated-orcid":false,"given":"Luisa","family":"Aring","sequence":"first","affiliation":[{"name":"Department of Nutritional Sciences University of Michigan School of Public Health  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun\u2010Kyung","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Nutritional 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