CHM and colonic neoplasm: Our observations that REP1 directly binds to FOXO3 proteins, and REP1-dependent cytoplasmic re-localization of FOXO3 is closely correlated with survival of colon cancer cells, are quite similar to the previously proposed mechanisms which show that nuclear-cytoplasmic shuttling of FOXOs is regulated by Akt and 14-3-3.45, 46 Taken together, these data indicate that REP1 is a novel regulator for nuclear-cytoplasmic shuttling of FOXO3, during which it regulates cell survival under stress or starvation condition.