EGFR on the cell surface is dynamic, undergoing continuous exo- and endocytosis. These processes are tightly controlled by many regulatory molecules; for example, SNAREs mediate membrane-fusion events during exocytosis, whereas adaptors such as AP-2 take part in endocytosis. Lydia Danglot, Thierry Galli and colleagues (p. 723) now uncover a new mechanism by which EGFR cell-surface expression and signalling are regulated. They show that knocking down of the v-SNARE TI-VAMP (also known as VAMP7) accelerates EGF-induced clathrin-mediated endocytosis of EGFR, thereby decreasing its cell-surface diffusion and impairing early EGFR signalling events. Rather than affecting EGFR endocytosis directly, TI-VAMP depletion disrupts the trafficking of cargo-containing vesicles from the Golgi to the cell surface. Notably, the trafficking of CD82 (a tetraspanin that regulates EGFR endocytosis) is impaired, leading to reduced cell-surface expression of CD82 when TI-VAMP is depleted. Finally, decreased cell-surface expression of CD82 correlates with increased recruitment of AP-2 clusters specifically following EGF stimulation, suggesting that enhanced recruitment of the endocytic machinery underlies accelerated EGFR endocytosis in TI-VAMP-depleted cells.