We study a family of endocytic adaptor proteins called epsins, which are central to a number of important diseases in humans, including atherosclerosis, diabetes, cancer, and obesity. We have developed novel conditional mouse strains that have aided in the detailed characterization of epsins and their regulators. Our genetic approach, combined with an arsenal of biochemical, molecular, and cellular techniques, has allowed us to elucidate the mechanisms of epsin-dependent dysfunction and develop clinically-relevant therapies.