AMER1 (APC membrane recruitment protein 1) is a crucial regulator of the canonical Wnt signaling pathway that acts as both a positive and negative modulator depending on cellular context 1. The protein functions by binding phosphatidylinositol 4,5-bisphosphate and translocating to the cell membrane, where it interacts with components of the β-catenin destruction complex. AMER1 promotes β-catenin degradation through ubiquitination mechanisms, specifically by binding to SLC7A11 and ferritin light chain (FTL) and recruiting β-TrCP1/2 for their degradation 2. Phylogenetic analysis reveals AMER1 belongs to a vertebrate-specific gene family that originated early in vertebrate evolution through whole genome duplications 1. Clinically, AMER1 is significant as a tumor suppressor gene with germline mutations causing osteopathia striata with cranial sclerosis and predisposing to Wilms tumor 3. AMER1 deficiency promotes colorectal cancer metastasis by inhibiting ferroptosis, allowing cancer cells to survive oxidative stress during hematogenous spread 2. Somatic AMER1 mutations occur in various cancers including colorectal tumors and are associated with poor prognosis in metastatic disease 4. The gene also shows involvement in meningioma development, suggesting broader tumor suppressor functions 5.