It is suggested that mutant eIF2B resulted in improper activation of unfolded protein response (UPR) in the condition of endoplasmic reticulum stress, which has been proven in fibroblasts or lymphoblasts from VWM patients, and oligodendrocytes from VWM mouse model [24–27]. This evidence concerns the gene EIF2B4 and leukoencephalopathy with vanishing white matter.