VSIG4 (V-set and Ig domain-containing protein 4; also Z39Ig) is a 45-50kD macrophage-specific protein that belongs to the B7 family of molecules. Its constitutive expression depresses unwarranted T cell activation. Human VSIG4 is 399 amino acids (aa) in length. It is a type I transmembrane (TM) glycoprotein that contains a 264 aa extracellular domain (ECD) (aa 20-283) and a 95 aa cytoplasmic region. The ECD contains one V-type (aa 21-131) and one C2-type Ig-like domain (aa 143-226). Mouse VSIG4 has no C2-type domain. Over aa 20-139, human VSIG4 is 82% aa identical to mouse VSIG4. Multiple splice forms exist in human that impact the ECD and TM segments. One isoform deletes aa 67-143, while two additional isoforms substitute two aa