Equine Leukemia Inhibitory Factor (LIF) is a multifunctional cytokine belonging to the IL-6 family—which includes IL-6, IL-11, oncostatin M (OSM), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1), cardiotrophin-like cytokine factor 1 (CLCF1), and IL-27—and signals through receptor complexes containing the shared gp130 subunit. In horses (Equus caballus), LIF binds to the LIF receptor (LIFR) in association with gp130, activating JAK/STAT3, MAPK, and PI3K signaling pathways that regulate cell survival, differentiation, immune modulation, and tissue repair. Equine LIF plays a key role in reproductive biology, particularly in endometrial receptivity, embryo implantation, and early embryonic development, making it highly relevant to fertility management and assisted reproductive technologies in equine breeding programs. LIF is also involved in hematopoiesis, neural cell maintenance, and modulation of inflammatory responses in conditions such as equine asthma, colitis, and musculoskeletal injury, where STAT3-driven signaling can influence tissue remodeling and repair. Dysregulated LIF expression may contribute to fibrosis or tumor progression in certain contexts. As both a regenerative and immunomodulatory cytokine, equine LIF is important in studies of reproductive success, stem cell biology, inflammatory regulation, and cytokine network dynamics. Characterization of equine LIF supports veterinary research aimed at improving reproductive efficiency, understanding inflammatory and fibrotic disease mechanisms, and advancing regenerative therapies in equine medicine.