Caspase substrates won't be defined by a four-letter code.

Inflammatory cell death can be mediated by the murine caspase-1 and -11. Genetic and cell biological data point to conflicting conclusions whether these caspases cleave the same substrates or use distinct mechanisms to mediate inflammation and cell death. Peptide screening and biochemical analysis by Gonzales Ramirez et al. now suggest caspase-11 specificity may be determined outside the known substrate motif and identifies substrates cleaved preferentially by caspase-1, providing new opportunities to uniquely target inflammatory caspases.