ExSPECKt the unexpected: NLRP3-caspase-8-dependent cell death in RBCs

Red blood cell (RBC) lysis can cause morbidity and mortality. However, the molecular mechanisms underlying RBC lysis are not fully characterized, limiting therapeutic options. In this issue of Cell, Chen et al. identify a crucial role for the NLRP3-ASC-caspase-8 complex in driving programmed lytic cell death in RBCs.