Model for cytoskeletal regulation of CD44 membrane organization. Interactions of the cytoplasmic domain with ERM proteins, ankyrin, and perhaps other adaptors link CD44 to spectrin and actin networks. These interactions cause CD44 to form tight clusters, most of which probably comprise two to three molecules. Disrupting the ERM-binding site does not detectably alter clustering, although spacing between molecules might increase slightly. Disrupting the ankyrin-binding site allows some CD44 molecules to coalesce into larger but looser clusters. Disrupting both binding sites markedly reduces clustering. See “Discussion” for details. d, distance.