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The ATP13A2 protein, found in lysosomal and late\u2010endosomal membranes, performs cellular functions such as iron\u2010chelating agent transport and intracellular iron homeostasis. Mutations in\n                    <jats:italic>ATP13A2<\/jats:italic>\n                    can lead to intracellular iron accumulation; however, whether KRS caused by an\n                    <jats:italic>ATP13A2<\/jats:italic>\n                    mutation falls under Neurodegeneration with Brain Iron Accumulation disorders has long been debated. The most fundamental reason is that magnetic resonance imaging (MRI) cannot identify iron deposits in the basal ganglia in all KRS cases. We hypothesize that analyzing iron deposition at the cellular level could be more sensitive in detecting varying levels of iron accumulation associated with different\n                    <jats:italic>ATP13A2<\/jats:italic>\n                    mutations, and it may be more useful when conventional MRI fails to detect iron, yields inconclusive results, or cannot be performed. We identified two new\n                    <jats:italic>ATP13A2<\/jats:italic>\n                    mutations (p.Leu518_Thr519del, and p.Leu939Pro) in this study and comparatively investigated the impacts of three distinct\n                    <jats:italic>ATP13A2<\/jats:italic>\n                    mutations (p.Pro474fs, p.Leu518_Thr519del, and p.Leu939Pro) using KRS patients' primary fibroblasts and MCF7 cells overexpressing these mutated ATP13A2 proteins to analyze if these different mutations of\n                    <jats:italic>ATP13A2<\/jats:italic>\n                    can cause differing levels of iron accumulation. Following the detection of iron deposits via Prussian blue staining and inductively coupled plasma mass spectrometry, the cell viability was assessed via MTT assay to ascertain the impact of iron accumulation. Each type of\n                    <jats:italic>ATP13A2<\/jats:italic>\n                    mutation led to iron accumulation; however, frameshift and deletion mutations resulted in more iron accumulation than the missense mutation. In addition, the transient overexpression of the wild\u2010type ATP13A2 attenuated the cell death caused by iron accumulation. This study demonstrated that different types of\n                    <jats:italic>ATP13A2<\/jats:italic>\n                    mutations are related to varying levels of iron accumulation and provided an explanation for the inconsistent perspectives on the association of KRS with iron accumulation.\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\/jnc70418-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.70418","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T10:02:58Z","timestamp":1775556178000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Clinical Evaluation of Three\n                    <scp>KRS<\/scp>\n                    Families and Cellular Analysis of Distinct\n                    <i>ATP13A2<\/i>\n                    Mutations Reveal Different Levels of Iron Accumulation"],"prefix":"10.1111","volume":"170","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6216-3768","authenticated-orcid":false,"given":"Ezgi","family":"Erterek","sequence":"first","affiliation":[{"name":"Molecular Biology\u2010Genetics and Biotechnology, Graduate School Istanbul Technical University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1872-941X","authenticated-orcid":false,"given":"Benan","family":"Temizci","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics Istanbul Technical University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u015eeyma","family":"Tekg\u00fcl","sequence":"additional","affiliation":[{"name":"Research Center for Translational Medicine, Neurodegeneration Research Laboratory Suna and Inan K\u0131ra\u00e7 Foundation, Ko\u00e7 University School of Medicine  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2168-3667","authenticated-orcid":false,"given":"Bilal","family":"\u00c7ak\u0131r","sequence":"additional","affiliation":[{"name":"Food and Agricultural Research Center Istanbul Sabahattin Zaim University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Nazl\u0131","family":"Ba\u015fak","sequence":"additional","affiliation":[{"name":"Research Center for Translational Medicine, Neurodegeneration Research Laboratory Suna and Inan K\u0131ra\u00e7 Foundation, Ko\u00e7 University School of Medicine  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat","family":"G\u00fcltekin","sequence":"additional","affiliation":[{"name":"Department of Neurology Erciyes University Faculty of Medicine  Kayseri Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuhal","family":"Yap\u0131c\u0131","sequence":"additional","affiliation":[{"name":"Department of Neurology Istanbul Faculty of Medicine, Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5150-5349","authenticated-orcid":false,"given":"Arzu","family":"Karabay","sequence":"additional","affiliation":[{"name":"Molecular Biology\u2010Genetics and Biotechnology, 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