The gene for TNFRSF12A was initially recognized as a fibroblast growth factor inducible immediate early response gene Fn14 in mouse NIH 3T3 fibroblasts. Human TNFRSF12A cDNA encodes a 129 amino acid residue type I transmembrane protein with a 27 aa signal peptide，a 53 aa extracellular domain，a 21 aa transmembrane domain and a 28 aa cytoplasmic domain. Human and mouse TNFRSF12A hold 82% aa sequence identity. TNFRSF12 is the tiniest member of the TNF receptor superfamily and has only one cysteine rich region in its extracellular domain. The TNFRSF12A cytoplasmic domain holds one TRAF binding motif which binds TRAFs 1，2，and 3. TNFRSF12A binds its ligand TWEAK/TNFSF12A with high affinity to initiate a signal transduction cascade which subject to the cell type，causes different cellular responses such as cell death，cell proliferation，and angiogenesis.
