Abstract: In eukaryotic cells, proteins and membranes are transported between successive compartments by vesicle trafficking. Since precise protein localization is crucial for a range of cellular functions, it is not surprising that vesicle trafficking plays a role in many processes, including cell division, signaling, development, and even gene expression. We recently found evidence that the yeast secretory pathway directly regulates the dynamics of a key cell survival process, the unfolded protein response (UPR). UPR activation requires the processing of the transcription factor encoding RNA HAC1. We showed that the small yeast GTPase Ypt1, which regulates endoplasmic reticulum-to-Golgi trafficking, associates with and controls the RNA stability of unspliced HAC1 under normal growth conditions. Other small GTPases of the Ypt family also interacted with the unprocessed RNA. Here we speculate about the possible mechanism behind this novel secretory pathway-dependent regulation of endoplasmic reticulum homeostasis.