CTNNB1 encodes β-catenin, a key downstream effector of canonical Wnt signaling 1. In the absence of Wnt ligands, CTNNB1 forms a destruction complex with AXIN1, APC, GSK3B, and other proteins that phosphorylates and ubiquitinates CTNNB1, leading to proteasomal degradation 1. Upon Wnt stimulation, CTNNB1 escapes degradation, accumulates in the nucleus, and acts as a coactivator for TCF/LEF transcription factors to activate Wnt-responsive genes 1. Beyond canonical Wnt signaling, CTNNB1 functions in cell adhesion as a component of E-cadherin complexes and regulates epithelial-mesenchymal transitions 2. CTNNB1 also acts as a negative regulator of centrosome cohesion and inhibits anoikis in malignant epithelial cells 34. CTNNB1 mutations contribute significantly to human malignancies. Aberrant CTNNB1 activation drives hepatocellular carcinoma development, with mutations conferring distinct phenotypes including low proliferation but immune exclusion 5. In endometrial cancer, CTNNB1 mutations alter Wnt pathway signaling to deregulate cell cycle genes, paradoxically showing low-risk histology but worse recurrence and survival outcomes 6. Heterozygous CTNNB1 mutations cause neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV), characterized by developmental delay and microcephaly 7. CTNNB1 mutations are also identified in diverse tumors including glomangiopericytoma and superficial fibromas 89.