Reports have also shown that sANPEP plays roles that are independent of its enzyme activity; for example, sANPEP acts as a ligand for a GPCR, which triggers the activation of the JNK, Src, and NF-κB pathways to upregulate the expression of cytokines and chemokines, such as IL-1β, IL-6, and MCP-1, thereby augmenting the infiltration of monocytes or macrophages seen in rheumatoid arthritis (28). This evidence concerns the gene CCL2 and rheumatoid arthritis.