Coat protein complex II (COPII) is associated with the trafficking of secretory proteins between the endoplasmic reticulum (ER) and the Golgi, promoting the accumulation of cargo proteins at ER exit sites (ERES) and the formation of the transport vesicles. However, the role of COPII in de novo cargo trafficking in mammalian cells is still controversial, as some studies have suggested that COPII-free vesicles transit to the Golgi. Here, Gia Voeltz and colleagues (Westrate et al., 2020) now demonstrate that secretory cargo can leave the ER in uncoated vesicles in a manner that is dependent on the GTPase Rab1. By adapting the retention using selective hooks (RUSH) system, the authors were able to analyse cargo trafficking from the ER in real time. They observed that COPII localises to ERES during vesicle formation, but remains associated to the ER upon vesicle release. However, exported vesicles that contain the secretory cargo are labelled by Rab1. Accordingly, expression of dominant-negative mutant forms of Rab1 blocks cargo export, but the amount of cargo at the ERES is not perturbed. These results point to a role for Rab1 in the extrusion mechanism, whereas COPII appears to regulate sorting and organization of the cargo at the ERES. This study thus not only identifies a new role for Rab1 in anterograde cargo trafficking, but also presents a new framework to study temporal and spatial dynamics of cargo transport from the ER.