Promotes apoptosis, possibly via a pathway that involves the activation of NF-kappa-B. Can also promote apoptosis mediated by BAX and by the release of cytochrome c from the mitochondria into the cytoplasm. Plays a role in neuronal apoptosis, including apoptosis in response to amyloid peptides derived from APP, and is required for both normal cell body death and axonal pruning. Trophic-factor deprivation triggers the cleavage of surface APP by beta-secretase to release sAPP-beta which is further cleaved to release an N-terminal fragment of APP (N-APP). N-APP binds TNFRSF21; this triggers caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6). Negatively regulates oligodendrocyte survival, maturation and myelination. Plays a role in signaling cascades triggered by stimulation of T-cell receptors, in the adaptive immune response and in the regulation of T-cell differentiation and proliferation. Negatively regulates T-cell responses and the release of cytokines such as IL4, IL5, IL10, IL13 and IFNG by Th2 cells. Negatively regulates the production of IgG, IgM and IgM in response to antigens. May inhibit the activation of JNK in response to T-cell stimulation. Associates with TRADD. Interacts with NGFR (By similarity). Interacts with N-APP. Detected in spleen B-cells (at protein level). Ubiquitous. Highly expressed in adult spleen, thymus, testis, prostate, ovary, small intestine, colon, brain, lung and kidney, and in fetal brain, liver and lung. Detected at lower levels in adult peripheral blood leukocytes, lung, and in fetal muscle, heart, kidney, small intestine and skin. Detected in T-cells, B-cells and monocytes. In T-cells expression is highest in Th0 cells, intermediate in Th2 cells and lower in Th1 cells. Expressed at low levels in proliferating progenitors in the spinal cord, but is highly expressed by differentiating neurons within the spinal cord and adjacent dorsal root ganglia. Expressed by developing neurons as they differentiate and enter a pro-apoptotic state. Expressed by both cell bodies and axons. No visible phenotype. Mice are born at the expected Mendelian rate, are viable and fertile. Mutant mice display an increased number of T-cells in the peripheral blood, but only a minor increase of the number of T-cells in spleen and thymus. T-cells from mutant mice show increased proliferative responses to antigens and produce higher levels of IL4, IL5, IL10, IL13 and IFNG. Mutant mice have normal serum levels of IgG and IgM in the absence of antigen, but produce higher levels of IgG, IgM and IgM in response to antigens. Likewise, B-cells from mutant mice display increased proliferation and decreased apoptosis in response to antigens. Mutant mice show increased levels of mature oligodendrocytes, decreased levels of apoptotic oligodendrocytes and increased myelination. Mutant mice are not susceptible to neuronal apoptosis triggered by exposure to amyloid peptides derived from APP. It is uncertain whether Met-1 or Met-25 is the initiator.