Unlike previous reviews, this paper integrates recent advancements in understanding the Nrf2/Keap1 (Kelch-like ECH-associated protein 1—nuclear factor (erythroid-derived 2)-like 2) axis, AGE-RAGE (advanced glycation end product–advanced glycation end-product receptor) signaling, and oxidative stress-induced immune dysregulation, highlighting their implications in RA pathophysiology. The gene discussed is KEAP1; the disease is rheumatoid arthritis.