Copy-number variation or mutations in the PLP-encoding gene, PLP1, result in pathological conditions, such as lethal Pelizaeus-Merzbacher disease (PMD) and milder spastic paraplegia type 2 (SP2), which both lead to CNS hypomyelination, hypotonia, ataxia, spasticity, and delayed development of motor and cognitive skills [20–23]. The gene discussed is PLP1; the disease is Pelizeaus-Merzbacher spectrum disorder.