The “O” subclass of FOX family consists of four proteins (FOXO1/FKHR, FOXO3/FKHRL1, FOXO4/AFX and FOXO6), which regulate cellular homeostasis, longevity and response to stress by modulating diverse cellular functions, including cell cycle, stress resistance, DNA damage repair, apoptosis, tumor resistance and metabolism (reviewed in [15,16,17]). The gene discussed is FOXO4; the disease is neoplasm.