Recently, FBXO7 has been demonstrated to alter proteasome activity leading to neuronal dysfunction [11], which could in part underlie the Parkinsonian pyramidal syndrome associated with loss-of-function mutations in FBXO7. However, an alternative mechanism has been proposed whereby FBXO7 can recruit PARKIN to the mitochondria and regulate mitophagy, such that mutated FBXO7 results in increased dysfunctional mitochondria and neuronal cell dysregulation [12]. Here, PRKN is linked to parkinsonian-pyramidal syndrome.