It is interesting to note that although the altered PANK2 activity causes perturbations in the expression of iron-sulfur cluster biosynthesis proteins such as NFS1, ISD11 and LYRM4, the clinical and neuroimaging findings in patients with PKAN and related disorders are quite different from primary disorders of Fe–S cluster biogenesis (globus pallidus involvement in PKAN versus the preferential leukoencephalopathy pattern seen in FE-S cluster biogenesis disorders) [12, 39]. This evidence concerns the gene NFS1 and Leukoencephalopathy.