Has the code for protein translocation been broken?

Polypeptides chains are segregated by the translocon channel into secreted or membrane-inserted proteins. Recent reports claim that an in vivo system has been used to break the "amino acid code" used by translocons to make the determination of protein type (i.e. secreted or membrane-inserted). However, the experimental setup used in these studies could have confused the derivation of this code, in particular for polar amino acids. These residues are likely to undergo stabilizing interactions with other protein components in the experiment, shielding them from direct contact with the inhospitable membrane. Hence, it is our view that the "code" for protein translocation has not yet been deciphered and that further experiments are required for teasing apart the various energetic factors contributing to protein translocation.