We have identified cornichon homologues (CNIHs) as novel auxiliary subunits of ionotropic glutamate receptors of the AMPA subtype (AMPARs). The isoforms CNIH2 and CNIH3 slow AMPAR gating and promote their surface expression in heterologous expression systems. Previously, CNIHs had been described as cargo exporters of soluble growth factors. Also in a recent study (Shi et al., 2010), the authors hypothesized that CNIHs predominantly function as endoplasmic reticulum (ER) chaperones of AMPARs. Here, we investigated where in the secretory pathway cornichons start to interact with AMPARs and how far they travel together. When expressed without AMPARs, CNIH2 is mainly localized in the Golgi complex and to a lesser extent in the ER. Experiments blocking the microtubuli-dependent anterograde shuttle between ER and Golgi complex indicate that CNIH2 behaves like a Golgi-resident protein, continuously cycling between Golgi and ER compartments. However, in the presence of AMPARs, CNIH2 escapes from this cycle and reaches the cell surface, both in heterologous expression systems and in neurons. Blocking selective ER export leads to a complete and specific loss of the CNIH-dependent increase in AMPAR surface expression, whereas inhibiting clathrin-dependent endocytosis does not, suggesting that CNIH promotes anterograde AMPAR trafficking by linking the receptor to the ER export machinery. In summary, these findings indicate that CNIHs interact with AMPARs early in the secretory pathway and promote their surface expression by facilitating their selective ER export. Additionally, we show that CNIHs and AMPARs interact not only in the ER, but stay together until they both reach the cell surface.