Recent advances in the study of protein translocation across the membrane of the endoplasmic reticulum include insights into the mechanism of signal-sequence function. Biochemical and genetic studies have provided further evidence that lumenal proteins perform direct roles in secretory protein translocation and in the regulation of protein-conducting-channel permeability during membrane protein integration. A hypothesis identifying the endoplasmic reticulum as a site of mRNA localization and compartmentalized protein synthesis has been suggested.