The aim of this study was to genetically and functionally characterize STAT4 in RA patients with different disease activity by analyzing two STAT4 variants (rs7574865 and rs11889341) in relation to gene expression, phosphorylated protein levels, and inflammatory cytokines such as IL-12, IL-23, and IFN-γ. This evidence concerns the gene STAT4 and rheumatoid arthritis.