It remains unclear whether promiscuity in β2-ARs in AA is confined to immune cells or extends to AR signaling in affected joint tissue, but understanding the extent to which signal switching or dual signaling cascade activation, as well as “when” and “where” promiscuous β2-AR signaling occurs in important disease-mediating targets is critical for understanding the pathophysiology of RA. Here, ADRB2 is linked to rheumatoid arthritis.