FAT1 is a member of the FAT atypical cadherin (FAT) subfamily of cadherin proteins. FAT1 is a single-pass transmembrane protein, first identified in a screen for tumor suppressor proteins in Drosophila. FAT1 is expressed primarily in epithelial cells, where it plays a prominent role in regulating cell growth and migration, in large part through the regulation of cell-cell adhesion dynamics. The intracellular cytoplasmic tail of FAT1 contains multiple functional motif/domains that regulate FAT1 functions, including a proline rich EVH1 binding motif that regulates actin cytoskeleton components (e.g., Ena/VASP proteins) at both cell-cell contact points and leading edges of migrating cells . FAT1 appears to play a role in linking cell adhesion events to intracellular signaling pathways. For example, FAT1 was capable of inhibiting the nuclear translocation of ?-catenin through its cytoplasmic FC1 domain interaction with ?-catenin, and activating the Hippo signaling pathway, suppressing YAP signaling by its N-terminal cytoplasmic region interaction with MST1 . Research studies have revealed that the tumor suppressor functions identified in Drosophila are conserved in vertebrate FAT1 homologs. For example, studies in human cancer cells showed that loss-of-function mutations in the gene encoding FAT1 promoted a hybrid epithelial-to-mesenchymal transition, which further enabled the development of cancer drug resistance. Notably, studies have also revealed an oncogenic function for FAT1 in some contexts.