V-set and immunoglobulin domain containing 4 (VSIG4) is a type I transmembrane glycoprotein that is a B7 family-related protein and an Ig superfamily member. Mouse VSIG4 is synthesized as a 280 amino acid (aa) precursor that contains a signal sequence, an IgV-type immunological domain (aa 36-115),one potential N-linked glycosylation site, and a single transmembrane domain. The IgV domain of mouse VSIG4 shares 86% and 80% aa sequence identity with the IgV domains of rat and human VSIG4, respectively. VSIG4 functions as a negative regulator of mouse as well as human T cell activation, and may be involved in the maintenance of peripheral T cell tolerance and/or unresponsiveness. VSIG4 acts as a macrophage complement receptor by binding complement fragments C3b and iC3b. VSIG4 binding to C3b inhibits complement activation through the alternative pathway, making it a potent suppressor of established inflammation.