Prior studies by us and others have shown, paradoxically, that modulating opposing responses in the UPR pathway, including inhibition of PERK or GADD34, leads to phenotypic benefit in PMD and other myelinating disorders (D'Antonio et al., 2013, Musner et al., 2016, Nevin et al., 2017). This evidence concerns the gene EIF2AK3 and Pelizeaus-Merzbacher spectrum disorder.