Interestingly, when a cross-species evolutionary analysis of side-chain conservation in the SNX5-related proteins is performed it is clear that the IncE peptide binds a hydrophobic surface groove that is strictly conserved in this protein family (Figure 7C). This very strongly implies that the site is normally engaged in a protein-protein interaction with an as yet unidentified binding partner(s) required for SNX5’s regular biological function, and that IncE is directly competing for this interface.