Here, for the first time, we showed that macrophages and FLSs can generate large amounts of ORM2, particularly when they are activated by proinflammatory cytokines and LPS, a Toll-like receptor 4 ligand, clearly demonstrating that these cells are major extrahepatic sources of ORM2 production and explaining the elevated ORM2 expression levels in RA joints. The gene discussed is ORM2; the disease is rheumatoid arthritis.