Calpains 1 and 2 (or µ and m) are ubiquitous calcium-activated proteases involved in pathological cardiovascular remodelling and development of inflammatory kidney diseases. Both proteases share many similar substrates and their activity is blunted by calpastatin, their natural, ubiquitous and specific inhibitor1. Since the deletion of both calpains 1 and 2 is lethal, we previously developed transgenic mice overexpressing rabbit calpastatin, which contains a substrate-like inhibitory sequence similar to mouse calpastatin (CalpTG mice)2. These mice have normal baseline calpain activity and phenotype and the increase in calpastatin expression has been shown previously to blunt specifically calpain activation in models of glomerulonephritis, sepsis, ischemia or pathological neo-angiogenesis2–5. Unlike synthetic inhibitors, calpastatin inhibits selectively calpains and not other proteases. Calpains promote inflammation onset through several mechanisms. They degrade IκBα on a specific PEST sequence, leading to NF-κB activation and pro-inflammatory cytokines production1, 6. In addition to cytokine transcription, calpains promote interleukin-1α (IL-1α) maturation and activation7. Calpains also limit glucocorticoid anti-inflammatory activity by degrading HSP-90 and are essential for inflammatory cell recruitment, migration and diapedesis1, 8, 9. Accordingly, calpastatin overexpression limits NF-κB activation and inflammatory cell migration10, 11.