Fusion of a synaptic vesicle with the plasma membrane is thought to be catalysed by the transmembrane regions (TMRs) of key synaptic and vesicular SNARE complex proteins that induce opening of a fusion pore, but this has not been tested physiologically. Zhou et al. show that, surprisingly, lipid-anchored SNARE proteins lacking TMRs can catalyse vesicle fusion. This suggests that the main function of the SNARE complex is to force the two membranes in close apposition, and that this is sufficient to induce membrane fusion.