Pelizaeus-Merzbacher disease (PMD) is the most common disease of hypomyelination disorder. Most of the patients displayed with development delay especially motor delay, nystagmus and hypotonia, and so on. PMD is caused by the pathological changes of oligodendrocyte cell, which end up with hypomyelination disorder. Previous studies have demonstrated PLP1 point mutation affects the survival of oligodendrocytes and the formation of myelin molecular structure by affecting the formation of PLP1/DM20 oligomerization: PLP1 duplication stops oligodendrocyte and myelin development. Recent studies on organelle interaction network (OIN) have further demonstrated the pathogenic mechanism of PLP1 mutations: point mutations impact oligodendrocyte myelination by affecting the trafficking of PLP1 mutants to the plasma membrane. While PLP1 duplication had closer ER-mitochondrion interfaces named mitochondria-associated membranes (MAMs). These changes in both the ER and mitochondria then led to mitochondrial dysfunction. At present, relevant studies have shown that some small molecular compounds or drugs such as cholesterol, piracetam and gene therapy can improve the clinical symptoms of PMD in animals, and their efficacy in PMD patients needs to be further confirmed.