The dickkopf (DKK)-related protein family is comprised of four central members, DKK-1 - 4, along with the distantly-related DKK family member DKK-L1 (Soggy), which is thought to be a descendent of an ancestral DKK-3 precursor due to its unique sequence homology to DKK-3 and no other DKK family member. DKK family members, with the exception of the divergent Soggy, share two conserved cysteine-rich domains and show very little sequence similarity outside of these domains. Playing an important regulatory role in vertebrate development through localized inhibition of Wnt-regulated processes, including anterior-posterior axial patterning, limb development, somitogenesis, and eye formation, DKKs have also been implicated post-developmentally in bone formation, bone disease, cancer, and neurodegenerative diseases. DKK proteins typically play an important regulatory role in the Wnt/β-catenin signaling pathway by forming inhibitory complexes with LDL receptor-related proteins 5 and 6 (LRP5 and LRP6), which are essential components of the Wnt/β-catenin signaling system. LRP5 and LRP6 are single-pass transmembrane proteins that appear to act as co-receptors for Wnt ligands involved in the Wnt/β-catenin signaling cascade. DKK-3 has been shown to potentiate, rather than inhibit, Wnt signaling through interactions with the high-affinity, transmembrane co-receptors Kremen-1 (Krm1) and Kremen-2 (Krm2). Recombinant Human DKK-3 expressed in