FOCAD (focadhesin) is a tumor suppressor gene located on chromosome 9.3 that functions as a critical stabilizer of the superkiller (SKI) complex, which performs mRNA surveillance at stalled ribosomes 1. FOCAD maintains proteostatic levels of SKI complex components SKIC2 and SKIC3, enabling proper mRNA degradation by the exosome complex 2. Loss of FOCAD compromises this mRNA quality control pathway, creating cellular vulnerability to downstream dependencies including PELO, TUT7, and HBS1L 134. Clinically, FOCAD dysfunction is associated with multiple disease contexts. Biallelic deletions cause severe congenital liver cirrhosis in infants, characterized by hepatocyte injury and fibrosis due to impaired mRNA homeostasis 2. Monoallelic germline deletions confer moderate predisposition to polyposis and colorectal cancer development 5, and FOCAD acts as a tumor suppressor in gastric cancer where it is downregulated and associated with poor prognosis 6. FOCAD loss in cancer creates synthetic lethal dependencies exploitable therapeutically: FOCAD-deleted tumors require PELO, TUT7/DIS3L2, or HBS1L for survival, suggesting these genes as promising therapeutic targets 134. Notably, rare FOCAD variants were identified in longevity studies, suggesting broader roles in aging pathways 7.