NFATC3 (nuclear factor of activated T cells 3) is a calcium-dependent transcription factor that regulates diverse cellular processes through direct transcriptional activation and repression. The protein translocates from cytoplasm to nucleus upon calcium influx and calcineurin activation, where it binds to specific DNA sequences to regulate gene expression 1. NFATC3 functions as a transcriptional activator by binding to target gene promoters, including VEGFR2 in glioblastoma cells where it promotes vasculogenic mimicry 2, and IL-8 in hepatocytes during cholestatic liver injury 3. In macrophages, NFATC3 serves a protective role by transcriptionally upregulating miR-204, which subsequently suppresses foam cell formation and atherosclerosis by reducing SR-A and CD36 expression 4. The protein also regulates human embryonic stem cell differentiation through interaction with c-JUN and control of SRPX2 expression 5. Clinically, NFATC3 shows therapeutic potential as its inhibition reduces cholestatic liver injury in mice 3 and atherosclerotic plaque formation 4. The protein's stability is regulated post-transcriptionally, as demonstrated by HNRNPA2B1-mediated mRNA binding that prevents protein degradation 2. NFATC3 represents a promising therapeutic target for metabolic diseases, given its role in macrophage polarization toward anti-inflammatory phenotypes 6.