Clathrin-mediated endocytosis is a major mechanism for internalization of proteins and lipids. Members of the connecdenn family, such as DENND1C, function as guanine nucleotide exchange factors (GEFs) for the early endosomal small GTPase RAB35 and bind to clathrin and clathrin adaptor protein-2. Thus, connecdenns link RAB35 activation with the clathrin machinery.