A novel NINJ1-mediated regulatory step is essential for active membrane rupture and common to different cell death pathways.

Plasma membrane rupture (PMR), the final event in lytic cell death that is in part responsible for the release of pro-inflammatory signals, was believed to be a passive event that followed osmotic swelling. Kayagaki et al. ¹ have discovered that PMR is, in fact, mediated by ninjurin-1 (NINJ1), adding a novel regulatory step that is conserved across different types of lytic cell death, such as pyroptosis, necroptosis, and apoptosis. PMR is dependent on NINJ1 oligomerization, which is mediated by its highly conserved putative N-terminal α-helix. In vivo data suggest that the NINJ1-dependent secretome that is released upon PMR is likely to modulate antimicrobial host defense, suggesting this additional regulatory step also has physiological relevance.