A similarly severe phenotype in mice with high Plp1/PLP1 transgene dosage (Kagawa et al., 1994; Readhead et al., 1994; Anderson et al., 1999) is associated with sequestration of PLP1 and cholesterol in endosomes/lysosomes (Simons et al., 2002) that, paradoxically, can be rescued by cholesterol supplementation in a mouse model (Saher et al., 2012), but not in PMD patients, likely due to differences in blood–brain barrier permeability between the two species in the context of this disease (Stumpf et al., 2019). The gene discussed is PLP1; the disease is Pelizeaus-Merzbacher spectrum disorder.