The Nuclear factor of activated T cells (NFAT) proteins play a pivotal role in the development and function of the immune system. For example, in T cells, NFAT proteins play a role in activation, thymocyte development, differentiation, and self-tolerance. NFAT is a family of transcription factors that is composed of five family members, NFAT1 (NFATp/NFATc2), NFAT2 (NFATc1), NFAT3 (NFATc4), NFAT4 (NFATx/NFATc3), and NFAT5. All NFAT family members contain a highly conserved DNA-binding domain that confers DNA binding specificity that is structurally related to the DNA binding domain of the Rel/NF-kB family of transcription factors. NFAT proteins 1-4 are regulated by calcium and by calcineurin, a serine/threonine phosphatase. In the cytoplasm, NFAT proteins are normally present in a highly phosphorylated form by the action of a number constitutive kinases. Activation of NFAT proteins occurs with the engagement of antigen receptors present on T cells which lead to the activation of phospholipase C-y (PLC- y), production of inositol-1,4,5-triphosphate (IP₃), diacylglycerol, and elevation of cytosolic Ca ²⁺. This in turn, leads to the activation of calcineurin, a serine/threonine phosphatase, which dephosphorylates and activates NFAT, which translocates from the cytoplasm to the nucleus. NFAT in conjunction with the activator protein 1 (AP-1) control the inducible expression of many target genes involved in immune regulation.

The development of inhibitors of NFAT, specially those that have low toxicity and improved specificity, may lead to a greater understanding of the regulation of NFAT proteins and development of potential drugs for immunosuppression.