In this issue, Liao et al. report on the cell mechanisms for the transport of membrane proteins across the endoplasmic reticulum (ER). Liao et al. found that the ribosome formed a tight seal with the translocon and that the lumenal and cytoplasmic sides of the translocon opened and closed at various points during protein synthesis. In this remarkably precise regulation, the switches in translocon status occurred less than 10 amino acids after the transmembrane segment was synthesized, even though about 35-40 amino acids are thought to be contained within the ribosome and apparently inaccessible to translocon components. Liao et al.'s data suggest that the ribosome has a role in transmembrane segment recognition.