LRP6 (Low-Density Lipoprotein Receptor-Related Protein 6) is a crucial component in the Wnt/β-catenin signaling pathway, functioning as a co-receptor alongside Frizzled receptors (Fzds) to activate this canonical pathway. It plays a vital role in embryonic development, cell proliferation, and is implicated in various human diseases. The stability of β-catenin, a key protein in the Wnt signaling cascade, is regulated by the presence of Wnt ligands. In the absence of Wnt signaling, β-catenin is targeted for degradation by a destruction complex. However, when Wnt ligands bind to the FZD/LRP5/6 receptor complex, it leads to the recruitment of Dishevelled (DVL) and the inhibition of β-catenin phosphorylation, resulting in its accumulation and nuclear translocation to activate Wnt target genes. LRP6 is also subject to regulation by inhibitory proteins such as Dkk1, Sclerostin (Sost), Wise, and ZNRF3, which modulate its activation by Wnt members. Overexpression and mutations in LRP6 have been detected in diseases including hypertension, atherosclerosis, hypercholesterolemia, and cancer, highlighting its significance in both developmental processes and disease pathogenesis.
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