Research Progress on NINJ1-Mediated Plasma Membrane Rupture Regulation of Pathogen Infection Process

Pathological events in a wide range of diseases, from severe infections to sterile inflammatory disorders. PMR serves as the terminal step that releases large quantities of damage-associated molecular patterns (DAMPs)-intracellular molecules that act as danger signals once outside the cell. These DAMPs can trigger strong inflammatory responses, and in many cases, may precipitate a cytokine storm, a hyperactive immune reaction that often amplifies tissue injury beyond the initial insult. For decades, scientists generally believed that PMR resulted from membrane pore-forming cell death, such as pyroptosis or necroptosis, which causes osmotic imbalance and passive membrane swelling. However, in recent years, it was discovered that Nerve Injury-Induced Protein 1 (NINJ1) mediates PMR through active oligomerization. This review first uses pathogen infection as a classical model to explore how multiple cell death pathways converge on plasma membrane rupture (PMR). Subsequently, we elaborate on the structure and function of NINJ1 as a core executor of PMR. Finally, we broaden our perspective from infection to other non-infectious but equally PMR-driven major diseases, and systematically evaluate the commonalities and prospects of NINJ1-targeted therapeutic strategies across different pathological scenarios. It is hoped that this will provide new insights for future researchers in this field.