FAT3 (FAT atypical cadherin 3) is a tumor suppressor gene that functions as an atypical cadherin involved in cell-cell adhesion and may play a role in neurite interactions during development. FAT3 is frequently mutated across multiple cancer types, with mutations occurring in 27% of esophageal squamous cell carcinomas when combined with other FAT family members 1. The gene acts as an upstream regulator in the Hippo signaling pathway, where increased FAT3 expression leads to downregulation of oncogenic YAP1 activity through upregulation of the YAP1 antagonist VGLL4 2. FAT3 mutations are associated with increased tumor mutational burden (TMB) in multiple cancers including esophageal cancer and lung adenocarcinoma 34. Clinically, FAT3 mutations demonstrate complex prognostic significance that varies by cancer type and co-mutation status. In esophageal cancer, FAT3 mutations correlate with poor prognosis and serve as an independent prognostic factor 3. However, co-mutation of FAT3 with LRP1B defines beneficial subgroups in endometrial cancer and lung adenocarcinoma, associated with improved immunotherapy response, enhanced immune infiltration, and better overall survival 54. FAT3 has also been identified as a candidate gene for adolescent idiopathic scoliosis 6.