APC2 is a cytoskeletal regulator that stabilizes microtubules and modulates actin dynamics through activation of Rho family GTPases. It also functions in Wnt signaling by promoting the degradation of β-catenin (CTNNB1), acting as a negative regulator of canonical Wnt pathway signaling. Functionally, APC2 localizes to the Golgi apparatus, actin filaments, and microtubules, suggesting roles in cell motility and adhesion 1. APC2 is implicated in multiple disease contexts. In cancer, aberrant Wnt/β-catenin signaling through APC2 dysfunction contributes to immune exclusion in non-T-cell-inflamed tumors across multiple cancer types 2. In thyroid cancer, the epigenetic modifier KDM1A suppresses APC2 transcription, promoting stemness and cancer progression via Wnt pathway activation; the selective KDM1A inhibitor GSK-LSD1 reverses this effect and enhances chemotherapy sensitivity 3. In esophageal squamous cell carcinoma, downregulation of APC expression through METTL3-mediated epitranscriptomic modification increases β-catenin signaling and correlates with poor prognosis 4. At the neurological level, recessive missense variants in APC2 associate with epilepsy without brain malformation; truncating variants correlate with more severe cortical dysplasia and developmental delay, suggesting genotype-phenotype correlation in neurological disease 5. Structurally, APC2 contains a zinc-binding module critical for maintaining the stability of the larger APC/C protein complex 6.