Therefore, combining our in silico and in vitro observation, we speculated that ITIH4 can promote RA progression via acting as a ligand for the CXCR4 receptor in RA synoviocytes, activating the CXCR4 signaling pathway, and further regulating the disease-promoting molecules such as phosphorylation of PI3/Akt complex, activation of JAK and Src kinases, phosphorylation of p65 complex and their associated pathways PI3/Akt/mTOR pathway, JAK/STAT pathway, Ras/Raf/MEK/ERK, and NF-κB pathway respectively [59]. This evidence concerns the gene PI3 and rheumatoid arthritis.