DR5, also known as TRAIL-R2, was discovered by two groups from EST data by seeking homologs of the TNFR1 death domain or the DR4 cysteine-rich domain (CRD). Two variants were found, one with a membrane proximal TAPE motif insertion. Like DR4, DR5's expression is broad. Unlike DR4, only one 4.4 kb transcript was detected. Similar to DR4, DR5 has a long signal peptide (51 amino acids), a CRD domain, and a death domain closely related to DR4.