This findings suggest that, in the TD model, PKR inhibition acts downstream of the initial abnormal pathways associated with the lack of vitamin B1 and that the neuroprotective and functional effects obtained with PKR inhibition could be more related to the lack of activation of intrinsic or extrinsic apoptotic pathways46 or by a late regulation of autophagy.48, 49. This evidence concerns the gene EIF2AK2 and thanatophoric dysplasia.