Transcriptional regulator which is crucial for the development and inhibitory function of regulatory T-cells (Treg). Plays an essential role in maintaining homeostasis of the immune system by allowing the acquisition of full suppressive function and stability of the Treg lineage, and by directly modulating the expansion and function of conventional T-cells. Can act either as a transcriptional repressor or a transcriptional activator depending on its interactions with other transcription factors, histone acetylases and deacetylases. The suppressive activity of Treg involves the coordinate activation of many genes, including CTLA4 and TNFRSF18 by FOXP3 along with repression of genes encoding cytokines such as interleukin-2 (IL2) and interferon-gamma (IFNG). Inhibits cytokine production and T-cell effector function by repressing the activity of two key transcription factors, RELA and NFATC2 (PubMed:15790681). Mediates transcriptional repression of IL2 via its association with histone acetylase KAT5 and histone deacetylase HDAC7 (By similarity). Can activate the expression of TNFRSF18, IL2RA and CTLA4 and repress the expression of IL2 and IFNG via its association with transcription factor RUNX1 (PubMed:17377532). Inhibits the differentiation of IL17 producing helper T-cells (Th17) by antagonizing RORC function, leading to down-regulation of IL17 expression, favoring Treg development (PubMed:18368049). Inhibits the transcriptional activator activity of RORA (By similarity). Can repress the expression of IL2 and IFNG via its association with transcription factor IKZF4 (PubMed:19696312). Homodimer. Dimerization is essential for its transcriptional regulator activity. Interacts with IKZF3 (By similarity). Interacts (via LXXLL motif) with isoform 4 of RORA (via AF-2 motif) (By similarity). Interacts with STUB1 and HSPA1A/B. Interacts with IKZF4, HDAC7 and KAT5. Interacts with RUNX1, RUNX2, RUNX3 and NFATC2. Interacts with RORC. Interacts with HDAC9 in the absence of T-cell stimulation (By similarity). Interacts with RELA, PPP1CA, PPP1CB, PPP1CG, HSPA8 and USP7 (By similarity). Predominantly expressed in the cytoplasm in activated conventional T-cells whereas predominantly expressed in the nucleus in regulatory T-cells (Treg) (By similarity). The 41 kDa form derived by proteolytic processing is found exclusively in the chromatin fraction of activated Treg cells. High level of expression in thymus and spleen. By TGFB1 in T-cells. Down-regulated in regulatory T-cells (Treg) during inflammation. The fork-head DNA-binding domain is essential for its dimerization and interaction with NFATC2. Acetylation on lysine residues stabilizes FOXP3 and promotes differentiation of T-cells into induced regulatory T-cells (iTregs) associated with suppressive functions (PubMed:22312127). Acetylation is mediated by a coordinated action of KAT5 and EP300/p300 acetyltransferases: EP300/p300 is required to enhance KAT5 autoacetylation, promoting acetylation of FOXP3 by KAT5 (By similarity). Deacetylated by SIRT1 (PubMed:22312127). Polyubiquitinated, leading to its proteasomal degradation in regulatory T-cells (Treg) which is mediated by STUB1 in a HSPA1A/B-dependent manner. Deubiquitinated by USP7 leading to increase in protein stability. Phosphorylation at Ser-418 regulates its transcriptional repressor activity and consequently, regulatory T-cells (Treg) suppressive function (By similarity). Phosphorylation by CDK2 negatively regulates its transcriptional activity and protein stability. Undergoes proteolytic cleavage in activated regulatory T-cells (Treg), and can be cleaved at either the N- or C-terminal site, or at both sites. Treg expressing the form cleaved at C-terminal site or both N- and C-terminal sites exhibit an increased induction of IL10 and an increased capacity to suppress proliferation of conventional T-cells in vitro. Treg expressing the form cleaved at only the C-terminal site are highly effective at preventing experimental colitis in an in vivo model of inflammatory bowel disease. Defects in Foxp3 are the cause of the scurfy phenotype (sf). It results in a lethal disorder of immunoregulation, characterized by infections, diarrhea, anemia, thrombocytopenia, hypogonadism, gastrointestinal bleeding, lymphadenopathy and leukocytosis.