Brain and reproductive organ-expressed protein (BRE) is a 415 amino acid protein which binds to the intracellular juxtamembrane domain of the death receptor, tumor necrosis factor receptor 1 (TNF-R1). BRE also binds to the death receptor, FAS. BRE downregulates TNFa-induced activation of NFkB and may play a role in homeostasis or cellular differentiation in cells of epithelial, neural and germ line origins. It inhibits components of the death-inducing signaling complexes that are necessary for activation of the mitochondria, thereby mediating apoptosis. BRE is strongly expressed in the adrenal cortex, medulla, testis and pancreas, and is weakly expressed in the thymus, thyroid, stomach and small intestine.