FOXO3 belongs to the O subclass of the forkhead family of transcription factors which are characterized by a distinct fork head DNA binding domain. There are three other FoxO family members in humans, FOXO1, FOXO4 and FOXO6. These transcription factors share the ability to be inhibited and translocated out of the nucleus (aside from FOXO6, which may be constitutively nuclear) on phosphorylation by proteins such as Akt/PKB in the PI3K signalling pathway. Other post-translational modifications including acetylation and methylation are seen and can result in increased or altered FOXO3a activity.

This protein likely functions as a trigger for apoptosis through upregulation of genes necessary for cell death, such as Bim and PUMA , or downregulation of anti-apoptotic proteins such as FLIP.