PKR can mediate Tau phosphorylation induced by Aβ exposure in cell cultures.17 Additionally, several investigators have demonstrated that eIF2α phosphorylation, via PKR-induced cellular stress, leads to increased BACE1 mRNA translation when, paradoxically, global protein translation is inhibited.18, 19, 20, 21 These alterations of BACE1 translational control could be explained by a stress-dependent phenomenon of translation initiation.22, 23, 24 Moreover, PKR and eIF2α are highly phosphorylated in SmTN and the cerebellum of TD mouse model. Here, BACE1 is linked to thanatophoric dysplasia.