The proposal that the secretory proteins are initially synthesised with an N-terminal sequence (the signal sequence or leader sequence), that assists it across the membrane of the rough endoplasmic reticulum where it is synthesized, but is cleaved from the protein by a signal peptide peptidase even before the synthesis of the protein is complete. Mitochondrial and chloroplast proteins that are synthesised on ribosomes also have signal sequences that target them to their organelle; these may be N-terminal or internal, and may or may not be removed by proteolysis.