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This neurodegenerative disorder is characterized by iron accumulation in the basal ganglia. Pantothenate kinase is the first enzyme in the biosynthesis of coenzyme A from pantothenate (vitamin B<jats:sub>5<\/jats:sub>). <jats:italic>PANK2<\/jats:italic>, one of four human pantothenate kinase genes, is uniquely predicted to be targeted to mitochondria. We demonstrate mitochondrial localization of PANK2 and speculate on mechanisms of secondary iron accumulation in PKAN. Furthermore, <jats:italic>PANK2<\/jats:italic> uses an unconventional translational start codon, CUG, which is polymorphic in the general population. The variant sequence, CAG (allele frequency: 0.05), leads to skipping of the mitochondrial targeting signal and cytosolic localization of PANK2. This common variant may cause mitochondrial dysfunction and impart susceptibility to late\u2010onset neurodegenerative disorders with brain iron accumulation, including Parkinson's disease.<\/jats:p>","DOI":"10.1196\/annals.1306.023","type":"journal-article","created":{"date-parts":[[2004,4,23]],"date-time":"2004-04-23T03:27:51Z","timestamp":1082690871000},"page":"282-298","source":"Crossref","is-referenced-by-count":102,"title":["Mitochondrial Localization of Human PANK2 and Hypotheses of Secondary Iron Accumulation in Pantothenate Kinase\u2010Associated Neurodegeneration"],"prefix":"10.1111","volume":"1012","author":[{"given":"MONIQUE A.","family":"JOHNSON","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YIEN MING","family":"KUO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SHAWN K.","family":"WESTAWAY","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SUSAN M.","family":"PARKER","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KATHERINE H. 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