FAT4 is a calcium-dependent atypical cadherin that functions as a tumor suppressor through multiple regulatory mechanisms. At the cellular level, FAT4 maintains planar cell polarity and regulates the Hippo-YAP signaling pathway, inhibiting neuroprogenitor proliferation 1. Mechanistically, FAT4 antagonizes Wnt/β-catenin pathway activation by binding β-catenin and promoting its phosphorylation and degradation, thereby suppressing PD-L1 expression and membrane localization in cancer cells 1. FAT4 expression is regulated by METTL14-mediated m6A RNA methylation in ocular melanoma, where restored FAT4 levels suppress tumor growth 2. In diabetic complications, METTL3-mediated m6A methylation represses FAT4 expression, impairing pericyte function and vascular integrity 3. FAT4 is targeted for ubiquitin-proteasome degradation by UBE4B in gastric cancer, promoting tumor progression 4. Additionally, FAT4 acts as a receptor for the p53-regulated tumor suppressor Reprimo, activating the Hippo-YAP/TAZ-p73 apoptotic pathway 5. Loss-of-function FAT4 mutations occur in ~27% of esophageal squamous cell carcinomas 6. FAT4 mutations cause periventricular heterotopia with associated neuronal hyperactivity 7, consistent with its developmental role in cortical organization and neurogenesis.