BPS2026 – Cell membrane rupture mediated by NINJ1

Ninjurin-1(NINJ1), a 16 kDa transmembrane protein, has emerged as a key regulator of various types of lytic cell death. Recently, we demonstrated that NINJ1 directly regulates plasma membrane rupture, with the density of NINJ1 on the plasma membrane inversely correlated with the membrane’s lysis tension. However, molecular mechanisms underlying NINJ1-mediated membrane rupture are still unclear, with several recent studies identifying apparently contradictory NINJ1 assembly pathways. Here, we identify factors that regulate the assembly of NINJ1 in the plasma membrane. These findings allow us to propose a unifying molecular model for NINJ1-mediated membrane rupture.