Wnt signaling pathway is involved in regulating multiple developmental events.LRP5/6,also known as Arrow in Drosophila,are co-receptors necessary for transducing Wnt signaling.Besides the ability of binding Wnt ligand,activity of LRP5/6 is also correlated with the ability of interaction with Axin-a scaffold protein that negatively regulates Wnt signaling-to inhibit Axin/GSK/β-catenin complex.Previous studies showed that binding of LRP5/6 with Axin strongly depend on the phosphorylation of intracellular domain of LRP caused by GSK3β and CK 1γ.How this phosphorylation is regulated and what proteins are involved in this progress remains elusive.To address this question,we searched novel binding partners of LRP5/6 by using endogenous immunoprecipitation.Several known proteins were found and a novel protein named Dy1 was identified.Dy1 belongs to a small protein family,which is conserved only in vertebrates.The functions of this protein family are so far poorly understood.Here we show that Dy1 is a component involved in Wnt signal transduction pathway.Our data demonstrate that Dy1 might direct LRP5/6 phosphorylation caused by GSK3,enhance the interaction between Axin and LRP5/6,and therefore activates the canonical Wnt signaling pathway.