Leukemia inhibitory factor (LIF) is a 20 kD protein that belongs to the IL-6 receptor family. It binds to a heterodimeric receptor composed of a type I transmembrane ligand-binding subunit, the LIF-specific subunit gp190 (LIFR), and the type I transmembrane signal transducing subunit gp130, shared with the other members of the IL-6 family. It especially signals through STAT3 and JAK kinases. LIF expression has been observed in various tissues including thymus, lung, and neuronal tissues. LIF displays diverse biological effects, but is best known for its ability to inhibit the differentiation of embryonic stem cells in mice and contribute to stem cell self-renewal. LIF can be upregulated by proinflammatory cytokines such as TNF-α and IL-17, and elevated levels of LIF have been found in cases of rheumatoid arthritis, neural injury, systemic inflammation, and tuberculosis. Human and mouse LIF share 79% sequence homology and exhibit cross-species activity. However, LIF inhibition of stem cell differentiation appears to be mouse-specific. It is involved in the induction of hematopoietic differentiation in normal and myeloid leukemia cells, induction of neuronal cell differentiation, regulator of mesenchymal to epithelial conversion during kidney development, and may also have a role in immune tolerance at the maternal-fetal interface. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.