Unlike other PMD point mutations where endoplasmic reticulum stress has been described as a pivotal physiopathogenic factor in the disease 40, 55, 69, an additional explanation for the excess of ROS is the mislocalization of PLP to mitochondrial membranes, as previously described 3, 29, where it may interfere with OXPHOS. Here, PLP1 is linked to Pelizeaus-Merzbacher spectrum disorder.