IFI27L1 (interferon alpha-inducible protein 27 like 1) is an interferon-stimulated gene with pro-apoptotic activity that localizes to mitochondrial membranes and functions as a molecular adaptor in intrinsic apoptotic signaling pathways. The protein exhibits structural similarity to avian IFI6 and plays roles in innate immune responses 1. In Alzheimer's disease, IFI27L1 represents a female-specific protective neuronal association linked to reduced tau pathology in the dorsolateral prefrontal cortex, identified through single-nucleus transcriptomic analysis of 2.84 million nuclei 2. The gene is enriched in immune-, inflammation-, and damage-related stress-response pathways relevant to neurodegeneration. IFI27L1 expression is significantly downregulated in major depressive disorder peripheral blood, correlating with aberrant immune infiltration patterns including altered T cell co-inhibition and dendritic cell abundance 3. The gene participates in cytokine receptor interaction and calcium signaling pathways implicated in immune dysfunction. Genome-wide association studies identify IFI27L1 variants (rs59775050) associated with waist circumference in African populations, suggesting roles in metabolic regulation 4. In acute myeloid leukemia, IFI27L1 serves as a regulatory T cell-related prognostic biomarker, where elevated expression correlates with increased Treg infiltration, immune escape, and resistance to immunotherapy 5.