The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is activated by tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL), and thus transduces cell death signal and induces cell apoptosis. Studies with FADD-deficient mice suggested that FADD, a death domain containing adaptor protein, is required for the apoptosis mediated by this protein.

Pan et al. (1997) found that, as with FAS, TNFR1, and DR3, overexpression of DR4 induced apoptosis. However, unlike the other 3 death receptors, DR4 did not use FADD  to transmit the death signal, suggesting the use of distinct proximal signaling machinery.