APC2 is a cytoplasmic protein that functions as a negative regulator of Wnt/β-catenin signaling and a modulator of cytoskeletal dynamics. Mechanistically, APC2 promotes rapid degradation of β-catenin (CTNNB1), thereby suppressing canonical Wnt pathway activation 123. Additionally, APC2 stabilizes microtubules and regulates actin fiber dynamics through activation of Rho family GTPases 4. Subcellularly, APC2 localizes to the Golgi apparatus, actin filaments, and occasionally microtubules, suggesting roles in cytoskeletal organization and cell adhesion 2. APC2 dysfunction is implicated in cancer progression. Across TCGA, APC2 mutations are enriched 3-fold in non-T-cell-inflamed tumors, where activated β-catenin signaling promotes immune exclusion 5. In esophageal squamous cell carcinoma, reduced APC expression via epitranscriptomic downregulation correlates with poor prognosis and enhanced β-catenin-mediated proliferation 6. Furthermore, APC2 methylation is significantly elevated in tobacco use disorder patients, suggesting epigenetic dysregulation in disease states 7. APC2 allelic imbalance occurs in 95% of ovarian cancers, indicating tumor suppressor function 2. Germline APC2 variants are associated with cortical dysplasia and intellectual disability, highlighting developmental importance.