Extended treatment with the ionophore monensin was shown to increase the levels of certain Golgi glycosylation enzymes and vesicle transport components (Oku et al., 2011). Monensin collapses sodium and proton gradients, and thus raises the pH and induces swelling of low pH compartments, including the Golgi complex. The authors identified a “Golgi apparatus stress element” (GASE) in the promoters of several Golgi resident proteins that was required for their upregulation. Further work identified TFE3, a basic helix-loop-helix transcription factor, which binds to the GASE (Taniguchi et al., 2015). They showed that under normal growth conditions, TFE3 was phosphorylated and remained cytoplasmic, but after monensin treatment, TFE3 was dephosphorylated and it was transported to the nucleus. The signaling pathway resulting in dephosphoylation of TFE3 remains to be determined. Nuclear translocation of TFE3 and transcription of GASE-containing genes was also activated when proteoglycan synthesis was inhibited or the CMP-sialic acid transporter was depleted (Taniguchi et al., 2015), suggesting that TFE3 regulation of Golgi homeostasis involves glycosylation. It will be interesting to see if this pathway is activated by increased flux of cargo during differentiation of secretory cells or trafficking of large cargo, or if different regions of the Golgi activate different stress response pathways, as recently proposed (Sasaki and Yoshida, 2015).