NFAT2 (Nuclear Factor of Activated T cells 2), also known as NFATc1, is a member of the NFAT family of transcription factors that plays critical roles in both immune and nervous systems. Originally characterized for its role in T-cell activation, NFAT2 has emerged as a key regulator of neuroinflammation, synaptic plasticity, neuronal survival, and neural development. The gene encodes multiple isoforms through alternative splicing, with the most abundant being NFAT2a and NFAT2b. In the brain, NFAT2 is expressed in neurons, astrocytes, and microglia, where it transduces calcium signals into gene expression changes that influence neurodegenerative processes. NFAT2 activity is tightly regulated by the calcium/calmodulin-dependent phosphatase calcineurin, making it a target of interest for therapeutic modulation in neurological disorders. [@macian2001][@nguyen2008]
NFAT2 functions as a calcium-dependent transcription factor with diverse roles across multiple organ systems. Its activity is primarily regulated through the calcineurin-NFAT signaling pathway.
NFAT2 plays complex roles in AD pathogenesis:
In PD, NFAT2 contributes to disease processes:
NFAT2 is implicated in MS pathophysiology:
Following cerebral ischemia:
NFAT2 demonstrates broad expression: