This knowledge is particularly relevant considering that the pathogenetic role of PERK mutations in a spectrum of diseases, including the Wolcott-Rallison syndrome (WRS; Julier and Nicolino, 2010), is increasingly linked to mitochondrial dysfunctions and aberrant lipid metabolism (Julier and Nicolino, 2010; Oberhauser and Maechler, 2021), which cannot be explained uniquely by its canonical role in the UPR. This evidence concerns the gene EIF2AK3 and Wolcott-Rallison syndrome.