In the canonical Wnt signaling pathway, in the absence of Wnt binding, β-catenin is sequestered by a destruction complex composed of GSK3β, Axin, APC, and CK1, leading to phosphorylation of β-catenin at serine/threonine residues. Phosphorylated β-catenin is then degraded by proteasomal degradation mediated by polyubiquitination, keeping the Wnt signaling inactive. When Wnt binds to its receptor complex, including the seven-transmembrane receptor Fzd and co-receptors LRP5 or LRP6, the Wnt/β-catenin pathway is activated. This binding mobilizes GSK3β and CK1 to the plasma membrane, where they phosphorylate serines on LRP5/6, promoting signal formation and recruitment of Dvl and Axin. β-catenin is released from the destruction complex, accumulates in the cytoplasm, and translocates into the nucleus where it binds to TCF/LEF to activate target gene expression, thus activating the Wnt signaling.