FOX (forkhead box) proteins are a family of transcription factors that play important roles in regulating the expression of genes involved in cell growth, proliferation, differentiation, and longevity. Many FOX proteins are important to embryonic development. FOX proteins also have pioneering transcription activity by being able to bind condensed chromatin during cell differentiation processes.

There are 50 different FOX genes encoding FOX proteins in humans that are further divided into 19 subdivisions based on conserved sequence similarity. The defining feature of FOX proteins is the forkhead box, a sequence of 80 to 100 amino acids forming a motif that binds to DNA. This forkhead motif is also known as the winged helix, due to the butterfly-like appearance of the loops in the protein structure of the domain. FOX proteins are a subgroup of the helix-turn-helix class of proteins.

FOX genes are key elements in many developmental and biological processes, including regulating the cell cycle, metabolism, apoptosis, immune control, and pluripotency of embryonic stem cells. Beginning in unicellular eukaryotes, FOX genes developed by means of duplication and evolutionary divergence to acquire specialized roles. By binding to particular DNA sequences, these proteins control gene expression and so affect cellular differentiation and organogenesis.

Many genes encoding FOX proteins have been identified. There are 50 FOX genes in humans, divided into 19 different subclasses from FOXA to FOXS, based on conserved sequences. These subdivisions have diverse functions across different tissues and biological processes and genes within a given subunit often exhibit functional similarities. For example, the FOXM genes encode proteins that are involved in cell cycle progression. FOXC genes encode proteins that ensure normal embryonic development and play a key role in the growth and function of different organs.

FOX proteins play an important role in apoptosis and function as tumor suppressors, removing damaged cells. This is done via a mitochondria-dependent pathway or a mitochondria-independent pathway. In the mitochondria-independent pathway, FOX proteins increase the expression of death receptor ligands such as Fas ligand (FasL) and TNF-related apoptosis-inducing ligand (TRAIL). In the mitochondria-dependent pathway, FOX proteins activate pro-apoptotic Bcl-2 family proteins.

FOXM1 is a well-defined transcription factor controlling genes linked to cell cycle development, preserving cellular homeostasis. FOXM1 promotes the entry of a cell into the S phase and ensures the cell undergoes mitosis properly. FOXM1 activity is regulated by proliferation and anti-proliferation signals. FOXM1 is a highly expressed tumour repressor in growing cells and contributes to tumorigenesis when dysregulated.^{[citation needed]} Phosphorylation events regulate FOXM1 activity by influencing its localization and transcriptional action.

The FOXO1 gene is involved in maintaining the pluripotency of embryonic stem cells. FOXO1 regulates critical pluripotency associated genes such as OCT4, NANOG and SOX2 (Oct4 and Sox2 are Yamanaka factors) by occupying and activating their promoters. This function can be inhibited by the ATK protein kinase. The FOXO genes also play a role in the regulation of metabolism. FOXO proteins translate insulin and growth factor signaling into physiological responses, including suppressing gene expression. FOXO1 is involved in promoting gluconeogenesis in the liver by interacting with PGC-1α. This interaction can be inhibited by phosphorylation events, where FOXO1 is removed from the nucleus.

Some FOX genes are downstream targets of the hedgehog signaling pathway, which plays a role in the development of basal cell carcinomas. Members of class O (FOXO- proteins) regulate metabolism, cellular proliferation, stress tolerance and possibly lifespan. The activity of FoxO is controlled by post-translational modifications, including phosphorylation, acetylation and ubiquitination.