NFATC1 is a transcription factor that plays central roles in immune cell activation and bone remodeling. In T cells, NFATC1 drives inducible expression of cytokine genes, particularly IL-2 and IL-4, and regulates T cell activation, proliferation, differentiation, and apoptosis 1. NFATC1 functions through the calcineurin-NFAT signaling cascade, where calcium-dependent phosphatase calcineurin dephosphorylates and activates NFATC1 for nuclear translocation and DNA binding 2. In osteoclasts, NFATC1 is the master regulator of osteoclastogenesis downstream of RANKL signaling. RANKL-responsive superenhancers and their associated enhancer RNAs regulate NFATc1 expression, which is essential for osteoclast differentiation 3. The long noncoding RNA MALAT1 suppresses osteoclastogenesis by blocking Tead3 protein from activating NFATc1 4. Reduced NFATC1 expression correlates with osteochondroma formation, suggesting NFAT signaling suppresses certain bone tumor development 5. Beyond bone and immune cells, NFATC1 regulates pathological processes including chemokine expression in colon cancer cells via CXCL8, promoting neutrophil recruitment 6, and controls P2X7 receptor expression in intervertebral disc degeneration 7. NFATC1 gene fusions with EWSR1 or FUS define a distinct class of vascular neoplasms with potential for local recurrence 8.