The described alterations of calcium homeostasis and the phenotypical and functional changes of circulating monocytes in RA lead us to hypothesize that the CaSR-dependent stimulation of macropinocytosis in RA monocytes contributes to initiation and perpetuation of the chronic inflammatory response in those joints due to the triggering of a cytokine cascade spearheaded by IL-1β, and followed by other myeloid cytokines (see Figure 2) (Rossol et al., 2012b; Jäger et al., 2020). Here, CASR is linked to rheumatoid arthritis.