Consequently, we propose that de-phosphorylation of p-eIF2α by pevonedistat will not only lead to ER stress/UPR-mediated cell death via increased protein translation in ALL as previously reported [4], but also enhances the translation rate of the short STIM1 5’-uORF resulting in down-regulation of STIM1 gene expression and alteration of the Orai1:STIM1 ratio. The gene discussed is STIM1; the disease is acute lymphoblastic leukemia.