Clathrin-mediated endocytosis is a major route for diverse cargo to enter the cellular endocytic pathway. New findings by Puthenveedu and von Zastrow (2006) suggest that certain cargo proteins, such as G protein coupled receptors that bind to PDZ domains, regulate their own targeting to a subset of clathrin-coated pits. Thus, cargo proteins may cause functional specialization of vesicle trafficking within the early endocytic pathway.