Effects either on binding avidity or on membrane structure and trafficking dynamics could underlie how the CTB subunit, and the other AB 5 toxins, evolved as pentameric structures. This and our other recent studies, however, show that the most fundamental function exploited by CT is to coopt an endogenous glycosphingolipid sorting pathway from the PM to the ER that is essential for toxin entry into the cytosol and the induction of disease.