Cytokine-like Factor 1 (CLF-1), also known as Cytokine Receptor-like Factor 1 (CRLF1), is a soluble receptor subunit and a member of the cytokine type I receptor family. It exhibits significant similarity to the IL-6 family of receptors. CLF-1 is 422 amino acids (aa) in length with a predicted molecular weight of 46.3 kDa. It contains an N-terminal immunoglobulin-like domain (aa 38-131) followed by two fibronectin-like domains (aa 134-229 and 234-334). It also has the four cysteine residues and WSXWS motif that are conserved among all members of the cytokine type I receptor family. These conserved regions are located in the first and second fibronectin-like domains, respectively. Human CLF-1 shares 95% aa sequence identity with the mouse and rat orthologs. It is predominantly expressed in adult spleen, thymus, lymph node, appendix, bone marrow, stomach, placenta, heart, thyroid, and ovary, as well as in fetal lung tissue. CLF-1 mRNA levels are up-regulated by the pro-inflammatory cytokines TNF-alpha, IL-6, and IFN-gamma. CLF-1 associates with the IL-6-type cytokine Cardiotrophin-like Cytokine (CLC) to form a heterodimer composite cytokine that competes with Ciliary Neurotrophic Factor (CNTF) for binding to the CNTF receptor complex. This CLC/CLF-1 heterodimer has been shown to promote survival of motor neurons. CLF-1 has also been shown to associate with the p28 subunit of IL-27 and regulate natural killer cell and T cell activity. Mutations in the CLF-1 gene are linked to both Crisponi and cold-induced sweating syndromes.