The location of elevated HtrA2/Omi varies in different inflammatory diseases, with higher concentrations of HtrA2 in rheumatoid arthritis (RA) synovial fluid (SF) than in osteoarthritis (OA) SF, which correlates with the number of immune cells in RA SF, and with the finding that treatment of RA FLS with an endoplasmic reticulum stress inducer resulted in the release of HtrA2/Omi from the mitochondria into the extracellular space [28]. This evidence concerns the gene HTRA2 and rheumatoid arthritis.