Targeting NINJ1-mediated cell rupture to treat inflammatory diseases

This is the authors' abstract. We don't add key points for this paper.

Cell death can terminate in plasma membrane rupture to release potent pro-inflammatory intracellular contents thereby contributing to inflammatory diseases. Cell rupture is an active process, mediated by the membrane protein ninjurin-1 (NINJ1) in pyroptosis, post-apoptosis lysis, ferroptosis, and forms of necrosis. Once activated, NINJ1 clusters into large oligomers within the membrane to initiate cellular lysis. Recent preclinical studies have demonstrated that inhibiting NINJ1 is a new strategy for treating immune-mediated diseases. Indeed, both small molecule inhibitors and neutralizing antibodies can target NINJ1 clustering to preserve plasma membrane integrity and mitigate disease pathogenesis. In this Perspective, we provide a summary of the current state of knowledge and recent developments in targeting cellular integrity during cell death through NINJ1 inhibition to treat inflammatory disease, with a focus on liver injury. As these NINJ1-mediated cell death pathways are pivotal in maintaining health and contribute to disease pathogenesis when dysregulated, the studies discussed within have broad implications across the immunologic basis of molecular medicine.