To further figure out the hidden mechanism of SPTBN1 in RA, a series of functional experiments were carried out and the results demonstrated that the reduced expressions of MMP2, MMP9, IL‐8, IL‐1β, IL‐6, and Bcl2 as well as increased levels of Bax and cleaved caspase3 in SPTBN1‐overexpressed RA‐FLSs were reversed by PIK3R2 depletion, revealing that SPTBN1 repressed the migration and inflammation and promoted the apoptosis of RA‐FLSs via binding to PIK3R2. Here, MMP2 is linked to rheumatoid arthritis.