NINJ1 targeting shows potential for multiple sclerosis and other neurological conditions but faces significant knowledge gaps

Photo by National Cancer Institute / Unsplash

Frontiers in Medicine Published May 30, 2026 Medically reviewed May 30, 2026 Study authors: Mengting Tian, Meicen Zhou, Shiping Li, Yi Qu DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

NINJ1 targeting shows promise but faces unclear CNS roles and cell-specific function gaps.

This narrative review explores the potential of NINJ1 targeting using monoclonal antibodies, functional peptides, and small-molecule inhibitors across a broad spectrum of neurological conditions. The scope includes multiple sclerosis, ischemic stroke, traumatic brain injury, spinal cord injury, neuropsychiatric disorders, and neurodegenerative diseases. No specific population, sample size, or setting details were reported in this source.

The authors synthesize that while NINJ1 inhibition is a promising area of investigation, substantial uncertainties remain. The review highlights that the exact function of NINJ1 within the central nervous system is not fully defined. Furthermore, critical knowledge gaps regarding how NINJ1 operates in specific cell types within the CNS have been identified as major barriers to progress.

Because the precise biological mechanisms are not yet clear, the review suggests that clinical translation is premature. The authors do not report specific adverse events, tolerability data, or primary outcomes because these details were not available in the underlying literature reviewed. Practice relevance is constrained by these fundamental scientific uncertainties.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedMay 2026

View Original Abstract ↓

Ninjurin1 (NINJ1) is a cell-surface molecule that has gained considerable attention for its role in mediating plasma membrane rupture (PMR). Originally identified as an adhesion molecule induced after nerve injury, NINJ1 is now recognized as a common terminal executor of PMR across multiple forms of lytic cell death, including pyroptosis, necroptosis, and ferroptosis. This function positions NINJ1 as a key link between cell death and inflammatory activation. However, the precise role of NINJ1 in the central nervous system (CNS) remains unclear. This review systematically outlines the molecular structure, expression, activation, and regulation of NINJ1, with a focus on its multifaceted roles in CNS disorders, including multiple sclerosis, ischemic stroke, traumatic brain injury, spinal cord injury, neuropsychiatric disorders and neurodegenerative diseases. We also highlight critical knowledge gaps, particularly regarding cell type–specific functions in the CNS. Finally, we evaluate therapeutic strategies targeting NINJ1 (including monoclonal antibodies, functional peptides, and small-molecule inhibitors) and their potential applications in neurological diseases. By integrating current evidence and identifying unresolved questions, this review aims to provide a foundation for future mechanistic and translational studies of NINJ1 in the CNS.