©2012 EUROPEAN MOLECULAR BIOLOGY ORGANIZATION EMBO reports 1

hot off the presshot off the press The endoplasmic reticulum (ER) is essential for the synthesis and folding of proteins that transport through the secretory pathway. ER stress is implicated in several diseases, including cancer, neu-rodegeneration, diabetes and inflammatory conditions. To cope with stress, cells acti-vate a complex signal transduction pathway known as the unfolded protein response (UPR), which integrates information about the intensity and duration of the stress, to adapt and recover ER homeostasis or trigger apoptosis of irreversibly damaged cells [1]. However, beyond individual cells, the UPR is important in maintaining the homeostasis of full organs, including the liver, pancrea