ATF4 and central nervous system cancer: have demonstrated that activation of the PERK/ATF4 axis leads to decreased proliferation and increased apoptosis of GBM cells in response to stimuli such as irradiation.[31] Our previous work, and that of others, has shown that IDH mutation enhances the sensitivity of glioma to ERS, resulting in apoptosis through the activation of the PERK/ATF4 arm.[32, 33] Furthermore, Lita et al. have reported that IDH mutation induces ER dilation, dysfunction of lipid metabolism, and apoptosis of glioma cells.[34] Fusakio et al.