Eukaryotes are endowed with signaling pathways that couple the burden of protein folding in the lumen of their endoplasmic reticulum (ER) to rectifying changes in gene expression, mRNA translation, and chaperone activity. This homeostatic adaptation, referred to as the unfolded protein response (UPR), has pervasive effects on cellular and organismal physiology. The UPR is tuned by the balance between unfolded proteins and chaperones. Reserve chaperones suppress UPR transducers via their stress-sensing luminal domains, but the underlying mechanisms remain unclear. In this new paper from the Ron lab, Neidhardt et al. uncover a structural basis for a long-standing concept: that unfolded proteins activate stress signaling by competing for limited chaperones. Studying AGR2 and IRE1β, they reveal how chaperone binding disrupts the assembly of the active state of the stress transducer, providing a detailed view of cellular stress regulation.