Dickkopf 3 (Dkk3) belongs to the Dkk family of proteins, which are secreted glycoproteins that regulate the canonical Wnt/β-catenin (“Wnt”) signaling pathway. Wnt signaling is an essential cellular communication pathway that mediates a diverse array of cellular and molecular activities in embryonic development, tissue homeostasis, and disease pathogenesis. The prototypic Dkk family member, Dkk1, has been well characterized as an essential modifier of Wnt signaling. In contrast, the function of Dkk3 was initially unknown because it was a weak regulator of Wnt signaling, and mice deficient in Dkk3 had only mild phenotypes (see below), despite its sequence similarity to the other Dkk genes. However, in recent years, new functions for Dkk3 have been identified in immune regulatory pathways, malignancies, and neurogenesis, raising the exciting possibility that Dkk3 is a critical regulator of these processes and may be an important novel...
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