ATF4 and Wolcott-Rallison syndrome: PERK mutations in humans cause Wolcott-Rallison syndrome, characterized by neonatal diabetes,11,12 and loss of PERK signaling in mouse models results in dysregulated liver glycogen content and increased hepatocyte death in high-sugar dietary conditions.13,14 In mice and fruit flies (Drosophila melanogaster), Atf4-mutant animals show lower body fat content, and ATF4−/− mice show greater resistance to fatty liver under high-dietary-intake conditions.6