Compositions and methods related to Wnt signaling regulation by Dickkopf (Dkk) polypeptides and Wnt-related diseases are disclosed. For example, compounds that Kind a Dkk or LRP polypeptide are disclosed. Compounds that disrupt binding of a Dkk polypeptide to an LRP polypeptide are also disclosed. Methods for using the described compounds and compositions are also disclosed.