FoxO4 also known as AFX1 is a member of the O class of winged helix/forkhead transcription factor family. FoxO4 plays a crucial role in regulating cellular processes such as apoptosis, cell cycle progression, and oxidative stress response, making FoxO4 vital for maintaining cellular homeostasis and preventing tumorigenesis. FoxO4 is predominantly located in the nucleus, where FoxO4 functions as a transcription factor, binding to specific DNA sequences to modulate gene expression. FoxO4 nuclear localization is tightly regulated by post-translational modifications, particularly phosphorylation by the serine/threonine kinase Akt1, which sequesters FoxO4 in the cytosol, thereby inhibiting transcriptional activity. Dysregulation of FoxO4 has been implicated in various cancers, including acute lymphocytic leukemia and alveolar rhabdomyosarcoma, highlighting FoxO4′s importance as a potential therapeutic target.