IL1A (interleukin-1 alpha) is a multifunctional cytokine constitutively present in nearly all resting non-hematopoietic cells that bridges innate and adaptive immunity 1. Upon binding to IL1R1 receptor with accessory protein IL1RAP, it forms a high-affinity receptor complex 23 that recruits adapter molecules including MYD88 and IRAK proteins, ultimately activating NF-κB and MAPK pathways (p38, p42/p44, JNK) 24. IL1A functions as a nuclear alarmin: when passively released during necrosis, it induces inflammation and alerts the host to injury 5. Notably, IL1A directly senses DNA damage and signals genotoxic stress independent of cell death 1. In cancer pathophysiology, IL1A release during necroptosis generates myeloid-driven immunosuppression that restricts anti-tumor immunity, and low IL1A levels correlate with positive patient outcomes in solid malignancies 6. IL1A also regulates senescence-associated secretory phenotype (SASP) through MTOR-dependent translation, promoting age-related pathologies including cancer 7. High IL1A expression in oral cancer associates with poor overall survival 8. In recurrent pericarditis, IL-1α-targeting therapy (rilonacept) significantly reduces recurrence risk compared to placebo 9. Genetic polymorphisms in IL1A show variable associations with disease susceptibility, including keratoconus and Graves' disease 1011.