The type III transforming growth factor β (TGFβ) receptor (TβRIII or betaglycan) is a TGFβ superfamily co-receptor. Loss of TβRIII expression occurs in a broad spectrum of human cancers including cancers of the breast, kidney, lung, ovary, pancreas and prostate. TβRIII suppresses cancer progression, in part, by reducing cancer cell motility. this TβRIII function is independent of its TβRIII signaling role, with TβRIII activating Cdc42 via its interaction with the scaffolding protein β-arrestin2 to re-organize the actin cytoskeleton, decrease directional persistence and inhibit random migration in both epithelial-derived cancer cells and normal epithelial cells. these studies contribute to a growing body of literature supporting essential and nonredundant roles for TβRIII and emphasize the importance of continued investigation of TβRIII and other signaling co-receptors.