Significance Exporting bulky molecules poses challenges for cells, since the membrane vesicles that transport normal-sized molecules may not be sufficiently large. The protein Tango1 allows transport vesicles to grow much larger to accommodate bulky cargo. It has been puzzling why many smaller cargos also fail to be transported when Tango1 is absent. We show that this is because bulky cargos “clog up” the transport system, resulting in a general traffic jam. Once the blocking, large cargo is removed, the jam resulting from missing Tango1 is resolved, and other cellular stress signals also subside. However, structural defects in the transport system remain, showing that these are due to a direct requirement for Tango1, independent of its function in transport as such.