Butyrophilin 2A2 (BTN2A2) is a widely expressed type I transmembrane glycoprotein that functions as a negative regulator of immune responses. Mature human Butyrophilin 2A2 consisits of a 233 amino acid (aa) extracellular domain with two immunoglobulin-like domains, a 21 aa transmembrane segment, and a 237 aa cytoplasmic domain. Alternative splicing generates additional isoforms of human Butyrophilin 2A2 that lack the first, second, or both Iglike domains as well as isoforms with substitutions and deletions in the cytoplasmic region. Within the immune system, Butyrophilin 2A2 is expressed on thymic epithelial cells, native B cells, splenic NK cells, dendritic cells, and peritoneal macrophages and is up-regulated with cell activation. Butyrophilin 2A2 inhibits T cell proliferation and activation and enhances the development of FoxP3+ regulatory T cells. Its up-regulation in the hippocampus is associated with schizophrenia.