NINJ1

NINJ1 encodes a cell-surface protein originally identified as a nerve injury-induced homophilic adhesion molecule that promotes axonal growth^[1]. Mechanistically, NINJ1 now defines an active execution step in plasma membrane rupture (PMR), where lytic cell death releases intracellular DAMPs that propagate inflammation^[2]. Structural studies show that NINJ1 oligomerizes into membrane-associated filaments or rings, enabling plasma membrane rupture during pyroptosis and other lytic cell death pathways^[3][4]. In ferroptosis models, NINJ1 oligomerizes after lipid peroxidation and controls plasma membrane integrity, cytosolic protein release, and DAMP release from macrophages and fibroblasts^[5]. Compared with the related isoform NINJ2, NINJ1 is functionally distinct because NINJ1, but not NINJ2, is required for LDH release downstream of GSDMD activation^[4]. Cryo-EM analysis further explains this isoform distinction by showing that NINJ2 is a close paralog that cannot mediate PMR despite structural relatedness to NINJ1^[6]. For experimental applications, anti-NINJ1 monoclonal antibodies block NINJ1 oligomerization and prevent PMR in mouse models, supporting NINJ1 inhibition as a practical tool for studying inflammatory tissue injury^[7].