Keeping goblet cells unstressed: new insights into a general principle.

The regulation of unfolded protein response (UPR) sensors has been studied for over 20 years, but IRE1β has remained a mystery. IRE1β is highly expressed in goblet cells: specialized epithelial cells that secrete mucus. Two articles in this issue show that IRE1β is held in an inactive state by the goblet cell-specific chaperone AGR2; upon dissociation of AGR2, IRE1β dimerizes and becomes active. This mechanism is reminiscent of the dynamic control by BiP of three other UPR sensors: IRE1α, PERK and ATF6.