Meanwhile, in RA patients with rheumatoid factor (RF) positive, the level of phosphorylated BTK was correlated with RF titer.237,238 BTK mediates bone resorption by RANK and regulates osteoclast proliferation and differentiation, which is the main factor in the pathophysiological level of BTK phosphorylation by peripheral B cells in RA patients.237,239 Therefore, BTK is one of the most attractive targets for treating autoimmune diseases including RA.240–243. This evidence concerns the gene BTK and rheumatoid arthritis.