Many signaling proteins, including the proto-oncogene Ras, require the covalent addition of a lipid chain for proper function. This prenylated protein is then earmarked for further proteolysis and methylation. In his Perspective, Gelb discusses two reports in this issue that illuminate how the lipid is initially attached to the protein [Park et al . ( p. 1800 )] and how the later proteolytic modifications are accomplished [Boyartchuk et al . ( p. 1796 )]