Therefore, various biological functions of S100 protein can be exerted through regulating the calcium ions under in vivo conditions.229 For example, S100 regulates protein phosphorylation, enzyme activity, cell proliferation, cell differentiation, inflammatory reaction induction, and protects cells from oxidative damage.225,229 Studies showed that the high expression of S100A4 associate with rheumatoid arthritis, kidney fibrosis, and cardiac hypertrophy.230,231 Garrett et al.232 reported several phenothiazines that block the activity of S100A4. Here, S100A4 is linked to rheumatoid arthritis.