Clathrin is the major protein component in the coat formed around pits and vesicles involved in receptor-mediated endocytosis. Clathrin forms a non-covalently bound triskelion structure composed of three heavy chains (192kDa each) and three light chains (23-25kDa each). A variety of proteins facilitate receptor-mediated endocytosis through association with clathrin-coated vesicles. Huntingtin interacting protein 1 (Hip1) is an actin-binding protein that interacts with Huntingtin protein, and has been implicated in vesicular transport defects found in Huntingtin's disease. Hip1 related protein (Hip1R) is another actin binding protein that contains an epsin NH2-terminal homology (ENTH)domain, three coiled-coil regions, a leucine zipper, and a talin-like actin binding domain. Hip1R mRNA is widely expressed, and Hip1R protein is enriched in the cell cortex and perinuclear region. The ENTH domain of Hip1R is required for binding to phosphatidylinositol-4,5-bisphosphate, and this complex is essential for clathrin-mediated endocytosis. In addition, Hip1R colocalizes with clathrin, AP-2 and endocytosed transferrin. Thus, Hip1R may facilitate interactions between clathrin-coated pits and actin during endocytosis.