SS-A/Ro52 (Ro52) protein is one of the targets of autoantibodies in Sjogren's syndrome and systemic lupus erythematosus. Ro52 structurally belongs to the RING-B-box/coiled-coil family, which appears to carry out diverse functions, but the physiological function of Ro52 remains largely unknown. Here, the authors demonstrate that hydrogen peroxide but not other oxidative stressors induced translocation of Ro52 protein from the cytoplasm to the nucleus and this phenomenon was attenuated by inhibition of MAP kinases, ERK in particular. These findings raise the possibility that SS-A/Ro52 may function as a hydrogen peroxide-selective, oxidative stress-sensitive signaling molecule that is activated via the MAP kinase pathway.