Ninj1, also known as nerve injury-induced protein 1, is a cell-surface protein with two transmembrane regions. It has an essential role in plasma membrane rupture (PMR) during lytic cell death, a process that releases damage-associated molecular patterns (DAMPs) and propagates the inflammatory response. PMR is involved in various cell death pathways such as pyroptosis, necrosis, and apoptosis [1].

Ninj1-/-macrophages showed impaired PMR in response to diverse inducers of cell death, unable to release intracellular proteins like HMGB1 and LDH. They died with a distinct ballooned morphology due to defective disintegration of herniations [1]. Ninj1-/-mice were more susceptible to Citrobacter rodentium infection, suggesting PMR's role in anti-bacterial host defence [1]. In liver injury models, inhibition of Ninj1 or Ninj1 deficiency ameliorated hepatocellular PMR, reducing serum levels of related enzymes and DAMPs, as well as neutrophil infiltration [2]. In the context of liver ischemia-reperfusion injury, Ninj1 deficiency protected mice, with decreased pro-inflammatory cytokine production in Kupffer cells and reduced neutrophil infiltration through the Ninj1/Dusp1 axis [3].

In conclusion, Ninj1 is a key mediator of PMR during lytic cell death, playing a crucial role in inflammation and host defence. Gene knockout mouse models have revealed its significance in disease conditions such as bacterial infections and liver injury, highlighting its potential as a therapeutic target in these areas.