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Updated: Feb 24, 2026

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
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Nerve Injury-Induced Protein 2 preserves lysosomal membrane integrity to suppress ferroptosis

Jin Zhang1, Miranda Bustamante1, Yang Shi1

  • 1Department of Surgical and Radiological Sciences, University of California Davis School of Veterinary Medicine.

Biorxiv : the Preprint Server for Biology
|February 23, 2026
PubMed

Insights

Nerve injury-induced protein 2 (NINJ2) maintains lysosome integrity, preventing iron leakage and ferroptosis. Loss of NINJ2 sensitizes cells to ferroptosis, offering a potential cancer therapeutic strategy.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Immunology

Background:

  • Nerve injury-induced protein 1 (NINJ1) mediates inflammatory cell death.
  • NINJ2, a NINJ1 relative, does not promote inflammation via plasma membrane rupture.
  • The specific role of NINJ2 in cellular processes remained unclear.

Purpose of the Study:

  • To investigate the function of NINJ2 in cellular homeostasis.
  • To determine NINJ2's role in lysosomal membrane integrity and ferroptosis.
  • To explore NINJ2's potential as a therapeutic target in iron-related cancers.

Main Methods:

  • Immunofluorescence to determine NINJ2 localization.
  • Co-immunoprecipitation to identify NINJ2 interacting proteins.
  • Lysosomal membrane permeabilization assays.
  • Measurement of cellular labile iron and ferritin expression.
  • Analysis of ferroptosis sensitivity upon NINJ2 manipulation.
  • Gene silencing (knockdown) experiments.

Main Results:

  • NINJ2 localizes to lysosomes and interacts with LAMP1.
  • Loss of NINJ2 leads to lysosomal membrane permeabilization and cytosolic iron leakage.
  • NINJ2 deficiency increases labile iron, decreases ferritin expression, and promotes ferritin degradation.
  • NINJ2-deficient cells exhibit increased sensitivity to ferroptosis-inducing agents.
  • NINJ2 knockdown reverses ferritin degradation upon LAMP1 knockdown.

Conclusions:

  • NINJ2 is crucial for maintaining lysosomal membrane integrity and preventing ferroptosis.
  • NINJ2 regulates cellular iron homeostasis by influencing ferritin stability.
  • Dysregulation of NINJ2 contributes to ferroptosis and may be implicated in chronic inflammation.
  • NINJ2 and ferritin overexpression in iron-addicted cancers suggest NINJ2 as a potential therapeutic target.

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