Unraveling the mechanisms of NINJ1-mediated plasma membrane rupture in lytic cell death and related diseases.

Plasma membrane rupture (PMR), the ultimate event during lytic cell death, releases damage-associated molecular patterns (DAMPs) that trigger inflammation and immune responses in the development of various diseases. Recent years have witnessed significant advances in understanding the PMR mediated by ninjurin1 (NINJ1) in different lytic cell death processes. NINJ1 oligomerizes and ruptures the membrane in pyroptosis and other lytic cell death, participating in the pathogenesis of multiple diseases. Although the membrane-permeabilizing function of NINJ1 is well recognized, the role of NINJ1 in different types of lytic cell death and its impact on multiple disease processes have yet to be fully elucidated. This review summarizes the latest advances in the mechanisms of NINJ1-mediated PMR, discusses the membrane-inducing activity of NINJ1 in different lytic cell death, explains the implications of NINJ1 in lytic cell death-related diseases, and lists the inhibitory strategies for NINJ1. We expect to provide new insights into targeting NINJ1 to suppress lytic cell death for therapeutic benefit, which may become a new strategy to control inflammatory cell lysis-related diseases.