DACT2 (dishevelled binding antagonist of beta-catenin 2) is a negative regulator of Wnt/β-catenin signaling that functions as a tumor suppressor across multiple cancer types. DACT2 antagonizes the canonical Wnt pathway and negatively regulates Nodal signaling, likely through promotion of receptor degradation 1. The gene is frequently silenced in human cancers via promoter hypermethylation, including gastric cancer (55.7% of cases), breast cancer (49.7%), colorectal cancer, and oral squamous cell carcinoma 1234. In gastric cancer, DACT2 methylation correlates with reduced expression, increased tumor invasion, and intravascular emboli, though paradoxically with improved chemotherapy response 1. In colorectal cancer, DACT2 downregulation associates with advanced tumor stage and poor prognosis 56. Restoration of DACT2 expression suppresses cancer cell proliferation, migration, and xenograft growth by inhibiting both canonical and noncanonical Wnt signaling 13. Recent evidence indicates DACT2 regulates Wnt signaling in mesenchymal progenitor cells to control osteogenic differentiation 7. The gene represents a promising epigenetic biomarker and therapeutic target; kaempferol-mediated DACT2 demethylation reduces colorectal cancer tumor burden 6.