DR6 (also known as TNFRSF21 or CD358) is an orphan receptor of the tumor necrosis factor (TNF) receptor superfamily. It controls cell death and differentiation in a cell-autonomous manner in different cell types including neurons, oligodendrocytes, endothelial cells, and immune cells (PMID: 29459438). DR6 has been shown to activate NF-κB and JNK, and induce cell apoptosis (PMID: 9714541). DR6 interacts with TRADD, which is known to mediate signal transduction of TNF receptors. It has been reported that APP binds DR6 to trigger axon pruning and neuron death via distinct caspases, indicating that DR6 might be involved in Alzheimer's disease (PMID: 19225519).