TNFRSF10B/DR5/CD262

TNFRSF10B/DR5/CD262 is a TRAIL-binding TNF receptor family death receptor that mediates caspase-dependent apoptosis through its cytoplasmic death domain^[1]. Mechanistically, DR5 activates FADD-dependent apoptotic signaling and can also activate the NF-κB pathway, linking receptor engagement to both death-domain signaling and transcriptional responses^[2]. In reovirus-infected cell models, TRAIL binding to DR5 and DR4 mediates apoptosis, while anti-TRAIL antibodies, soluble TRAIL receptors, FADD inhibition, and caspase-8 inhibition block this process^[3]. In non-small cell lung cancer, 11 of 104 tumors carried TRAIL-R2 mutations in the death domain, supporting disease-focused evaluation of DR5 signaling integrity^[4]. Compared with related TRAIL receptors, DR5 shares TRAIL-dependent apoptotic function with DR4, whereas DcR1, DcR2, and osteoprotegerin lack equivalent apoptosis initiation capacity and can act as decoy receptors^[5]. Compared with DR5 transcript variants, long and short TRAIL-R2/KILLER/DR5 mRNA isoforms are both expressed in human tissues and cell lines, with the long form generally predominating^[6]. For experimental applications, conatumumab is a fully human agonist antibody to human DR5 that induces caspase activation and apoptosis in multiple tumor models^[7].- DR5 links TRAIL receptor engagement to FADD, caspase-8, and apoptosis pathway analysis^[2][3]. - DR5 isoform assessment should distinguish long and short TRAIL-R2/KILLER/DR5 transcripts^[6]. - DR5 agonist antibodies support mechanism studies of receptor clustering, caspase activation, and tumor apoptosis^[7].