Missense EIF2B5 gene variants are the most frequent observed genetic defect in VWM (Deng et al., 2021), and are thought to impair the function of the eIF2B complex by disrupting its guanine nucleotide exchange activity, which is essential for recycling eIF2-GDP to eIF2-GTP during protein translation initiation. This evidence concerns the gene EIF2B1 and leukoencephalopathy with vanishing white matter.