LETM1 and Wolf-Hirschhorn syndrome: Addressing the hypothesis that LETM1 dosage affects seizure propensity in WHS patients began with the acquisition of a basic structure-function understanding of the protein: using an EGFP-tagged human LETM1 construct transfected into HEK293 cells, Schlickum et al. corroborated the mitochondrial localization reported by Nowikovsky et al. Moreover, a 167-amino acid deletion at the amino terminus of LETM1 revealed this segment to be the mitochondrial targeting sequence of the protein (Schlickum et al., 2004).