Nerve injury-induced protein 1 (NINJ1) (NINJ1)

Nerve injury-induced protein 1 (NINJ1) is a small, two-pass transmembrane protein that has recently been identified as the essential mediator of plasma membrane rupture (PMR) during lytic cell death, including pyroptosis, necrosis, and apoptosis (Kayagaki et al., Nature 2021). While it was originally characterized as a cell adhesion molecule involved in nerve regeneration and axonal growth, its primary pathological role is the formation of large, non-selective pores that physically disrupt the cell membrane (D'Souza et al., Nature 2023). This rupture allows for the explosive release of pro-inflammatory damage-associated molecular patterns (DAMPs), such as IL-1β and HMGB1, which drive systemic inflammation and tissue damage. Consequently, NINJ1 is a high-priority therapeutic target for treating inflammatory conditions like sepsis, liver injury, and autoimmune diseases. Therapeutic strategies currently under investigation include monoclonal antibodies that block NINJ1 oligomerization and nucleic acid-based therapies, such as siRNA or antisense oligonucleotides, designed to target NINJ1 mRNA and reduce protein expression (Borges et al., 2022). By preventing membrane lysis rather than just inhibiting specific cytokines, targeting NINJ1 offers a broader approach to controlling inflammation.

Other names

Ninjurin-1NINJ1Nerve injury-induced protein 1

Inhibition of NINJ1 protein oligomerization to prevent plasma membrane rupture or degradation of NINJ1 mRNA to reduce protein synthesis.