It is of note that CACH/VWM disease is strongly associated with stress: (a) myelin loss and associated neurological symptoms of human patients deteriorate upon exposure to various stressors [4], [5], [6], [34]; (b) the unfolded protein response (UPR) pathway was found to be activated in the brains of CACH/VWM patients [35], [36]; (c) primary cultured fibroblasts isolated from CACH/VWM patients, as well as oligodendroglia derived-cell line expressing mutated eIF2B, are hypersensitive to induced ER stress [37], [38]; and (d) Eif2b5-mutated mice fail to recover from induced demyelination [10]. Here, EIF2B5 is linked to leukoencephalopathy with vanishing white matter.