Leukoencephalopathy with vanishing white matter (VWM) is an autosomal recessive leukoencephalopathy caused by any of EIF2B 1-5 mutations, encoding five subunits α-ε of eukaryotic translation initiation factor 2B (eIF2B). The clinical phenotype of the disease varies greatly. The typical manifestation is progressive motor function regression, which can be accompanied by ataxia and epilepsy and susceptible to episodic aggravation of stress such as fever and trauma. Imaging showed progressive liquefaction of cerebral white matter. Autopsy neuropathology is characterized by extensive white matter sparseness and cystic degeneration, no reactive proliferation of glial cells, abnormal astrocyte morphology, overexpression of progenitor cell markers Nestin and GFAPδ, and increased number of oligodendrocyte precursor cells and decreased mature oligodendrocytes, foamed and increased apoptosis. The VWM gene EIF2B 1-5 is housekeeping gene, but most patients usually only have white matter involvement. A small number of fetal and early infantile patients may have multisystem involvement, and adult female patients may have ovarian dysfunction. It is currently believed that astrocytes play a central role in the pathogenesis of VWM. Pathological astrocytes cause secondary oligodendrocyte maturation disorder and abnormal myelination, which in turn lead to white matter lesions. Other disease mechanisms, including excessive activation of the unfolded protein response (UPR) after endoplasmic reticulum stress, mitochondrial dysfunction, and autophagy inhibition, are not fully understood.