IFI27L2 (interferon alpha inducible protein 27 like 2) is an interferon-stimulated gene with dual roles in apoptosis and neuroinflammation. As a pro-apoptotic protein, IFI27L2 localizes to mitochondria and functions as a BH3-like protein that sensitizes cells to apoptotic stimuli 1. The protein contains putative Bcl-2 homology motifs enabling interaction with anti-apoptotic regulators and can form homodimers, suggesting involvement in mitochondrial pore formation during apoptosis 1. Beyond its intrinsic apoptotic function, IFI27L2 acts as an extracellular cytokine promoting neuroinflammation. Elevated circulating IFI27L2 associates with systemic inflammation and increased brain interleukin-1β expression 2. Recombinant IFI27L2 treatment of microglial cells induces pro-inflammatory cytokine production through NLRP3 inflammasome activation, reactive oxygen species generation, and metabolic reprogramming toward glycolysis 2. Clinically, IFI27L2 dysregulation appears significant in cancer and neurodegeneration. High IFI27L2 expression correlates with improved survival in prostate adenocarcinoma 3, while elevated plasma IFI27L2 is detected in stroke patients 2. These findings suggest IFI27L2 represents a potential therapeutic target for modulating both apoptosis and microglia-mediated neuroinflammation.