The cytokine TNF-α is a major drug target for rheumatoid arthritis, an
inflammatory joint disorder. An alternative approach is to target the protease
TNF-α convertase (TACE), which releases TNF-α from cells.
However, because TACE cleaves other proteins involved in development and cancer, a
tissue-specific inhibition of TACE in immune cells appears mandatory. In this issue
of the JCI, Issuree et al. report that iRHOM2 is a TACE activator in
immune cells. Loss of iRHOM2 largely protects mice from inflammatory arthritis,
making iRHOM2 a potential drug target for this condition.
