The activity of FOXO1 is tightly regulated by post-translational modifications, primarily phosphorylation, acetylation, and ubiquitination. For instance, Protein Kinase B (AKT) can phosphorylate FOXO1, leading to its exclusion from the nucleus and subsequent inactivation. Conversely, dephosphorylation allows FOXO1 to translocate into the nucleus, where it can bind DNA and activate target gene transcription.