DKK-1 (Dickkopf WNT signaling pathway inhibitor 1) is a member of the DKK protein family. Other members of this family include DKK-2, DKK-3, and DKK-4. The DKK family proteins share 35-40 % homology between various members. Recombinant human DKK-1 expressed in HEK293 cells is a 35-45kDa glycosylated protein. It is a secreted protein that functions as a negative regulator of Wnt/?-catenin signaling pathway. Wnt/ ?-catenin signaling pathway involves binding of the Wnt ligands to the seven-transmembrane receptor, Frizzled, and the coreceptor lipoprotein-related protein 5 and 6 (LRP5/6). DKK1 forms a ternary complex with LRP5/6 and another receptor, Kremen, followed by endocytosis of this complex and removal of LRP5/6 from the cell surface. It has been suggested that DKK-1 permits anterior development by inhibiting Wnt/ ?-catenin signaling, which is essential for posterior patterning in vertebrates. The balance between Wnt signaling and DKK-1 inhibition is critical for bone formation and homeostasis and insufficient or excess DKK-1 activity in bone results in increased or decreased bone density, respectively. (PMID: 17143291; 12050670; 10570958)