Xenopus Dickkopf (Dkk)-1 was initially discovered as a Wnt antagonist that plays an important role in head formation. By far, four members of Dkk have been identified in mammals. Each Dkk molecule contains two conserved cysteine-rich domains. Recent studies showed that the second Cys-rich domains of Dkk1 and Dkk2 inhibited Wnt-3a-activated signaling, whereas the first Cys-rich domains had no effects. In addition, the second Cys-rich domain of Dkk-2, but not that of Dkk-1, was able to activate the canonical pathway in the presence of LRP6, and this LRP-dependent signaling does not require Dvl.