Ferret (Mustela putorius furo) and Mink (Neovison vison) Leukemia Inhibitory Factor (LIF) are highly conserved and share identical protein sequences, reflecting their close phylogenetic relationship within the Mustelidae family. 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 both species, 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. Ferret and mink LIF are likely involved in reproductive biology, including endometrial receptivity and embryo implantation, as well as in hematopoiesis and neural cell maintenance. In health and disease, LIF-mediated STAT3 signaling may influence inflammatory responses during respiratory viral infections (notably influenza and SARS-CoV-2 in ferrets) and Aleutian disease virus or respiratory infections in mink, where regulation of tissue repair and immune balance is critical. Dysregulated LIF expression could contribute to fibrosis, chronic inflammation, or tumor progression. Because ferrets and mink are important models for respiratory viral pathogenesis and immune-mediated disease, characterization of their identical LIF supports comparative investigations into IL-6 family signaling, cytokine-driven tissue remodeling, and development of targeted STAT3-modulating therapies relevant to both veterinary and human medicine.