Cardiotrophin-like cytokine factor 1 (CLCF1)

Cardiotrophin-like cytokine factor 1 (CLCF1) is a secreted cytokine belonging to the interleukin-6 (IL6) family[1][3][4]. It functions primarily as a neurotrophic and immunomodulatory protein, forming a biologically active heterodimer with cytokine receptor-like factor 1 (CRLF1)[2][3][4]. The CLCF1/CRLF1 complex binds to the ciliary neurotrophic factor receptor (CNTFR) complex, activating downstream JAK/STAT3 signal transduction and influencing cell development, especially in the nervous and immune systems[3][4][6]. CLCF1 promotes neuron survival, regulates sweat gland function, and is a potent stimulator of B cells and hematopoietic progenitors, particularly favoring myeloid differentiation[7]. Mutations in CLCF1 cause cold-induced sweating syndrome 2 (CISS2), a rare genetic disorder affecting thermoregulation and development[4][5]. CLCF1 has no currently documented therapeutic drugs targeting it directly; its utility as a biomarker in clinical practice remains investigational.

Other names

Novel neurotrophin-1NNT-1B cell-stimulating factor 3BSF-3CISS2NR6

Binds as a heterodimer (with CRLF1) to the ciliary neurotrophic factor receptor (CNTFR) complex (CNTFRα, LIFRβ, gp130), activating JAK/STAT signaling[3][4][6] Induces phosphorylation of STAT3 and gp130 subunits[1][6] Indirectly promotes production of other hematopoietic and inflammatory cytokines (IL-6, G-CSF, IL-1β, IL-10, VEGF)[7]