Although it is difficult to rule out effects on synovial macrophages or immune cells after intraarticular injection of Ad-PLCη2 in CIA mice, the results of this study demonstrated that PLCη2 and its C2 domain bind to the key upstream signaling molecule HRAS, inhibiting its activity and broadly suppressing pathways such as the NF-κB, MAPK and JAK–STAT pathways, primarily in RA FLSs. Here, HRAS is linked to rheumatoid arthritis.