Recent studies revealed that GSDMB has alternatively spliced variants, with the non-pyroptotic variants inhibiting the pyroptotic ones.23,24 Motivated by this trans inhibition mechanism, we tested a panel of GSDME N-terminal domain mutants, including some associated with cancer,21 and identified I217N as defective in inducing pyroptosis and capable of inhibiting the wildtype counterpart (Figure S3A). Here, GSDME is linked to cancer.