FAT1 is an atypical cadherin that functions as a tumor suppressor through regulation of cell-cell adhesion and the Hippo signaling pathway. Mechanistically, FAT1 localizes to cell-cell junctions and focal adhesions where it interacts with Hippo pathway components including MST1 1. Loss of FAT1 function impairs this interaction, leading to YAP/TAZ nuclear translocation and activation of pro-tumorigenic transcription factors. FAT1 mutations are among the most frequent genetic alterations in human cancers. In squamous cell carcinomas, FAT1 deletion promotes tumor initiation, progression, and metastasis by inducing a hybrid epithelial-mesenchymal transition (EMT) state through activation of the CAMK2-CD44-SRC axis, YAP1 nuclear translocation, and ZEB1/SOX2 expression 2. FAT1 loss also drives drug resistance mechanisms: in breast cancer, FAT1 mutations promote CDK4/6 inhibitor resistance via Hippo pathway-mediated CDK6 upregulation 3, while in head and neck squamous cell carcinoma, FAT1 mutations associate with immunotherapy resistance 4. Beyond cancer, FAT1 has emerged as a target antigen in membranous nephropathy, an autoimmune kidney disease characterized by IgG immune complex deposition 56. FAT1 represents an important example of how cadherin-mediated cell adhesion and Hippo signaling intersect to control both tumor suppression and immune tolerance.