Dengue, a mosquito-borne viral disease, is a major public health concern in tropical regions. Clinical manifestations range from flu-like symptoms to the more severe dengue hemorrhagic fever (DHF), and there are currently no vaccines or specific medications to treat the infection. The disease is caused by a group of related, but antigenically distinct, enveloped single-stranded RNA viruses (DENV). In infected cells, viral particle assembly takes place in the endoplasmic reticulum (ER). The two structural glycoproteins E and prM are integrated into the lipid envelope of the nascent virion in the ER lumen, and the particles are then trafficked through the cis- and trans-Golgi network. There, the 'pr' propeptide of prM is cleaved to yield mature DENV particles, which are then released. However, little is currently known about host factors involved in DENV egress. Production of recombinant subviral particles (RSPs) upon ectopic expression of prM and E in cells provides a safe, convenient model system to study virus secretion. This system was previously used to demonstrate that depletion of Arf4 and Arf5, two small GTPases involved in the formation of trafficking vesicles, results in entrapment of RSPs in the ER. Interestingly, depletion of Arf4 and Arf5 also inhibits the retrograde cycling of KDEL receptors (KDELRs), proteins involved in the retention of resident soluble proteins in the ER lumen. Therefore, Bruzzone, Wang and colleagues investigated the involvement of KDELRs in DENV trafficking and found that siRNA-mediated knockdown of these receptors reduced release of RSPs and DENV from cells. Moreover, KDELRs colocalized with prME in DENV-infected or prME-expressing cells, thus suggesting a possible physical interaction. Biochemical analyses indeed showed that prM interacts with KDELRs through its N-terminal pr peptide in the ER. Mutagenesis identified amino acid residues in prM that mediate KDELR binding in vitro. Functionally, mutation of these residues did not inhibit RSP assembly in the ER but did reduce particle trafficking to the cis-Golgi. The authors thus define a new intracellular receptor required for DENV egress and show that host factors play a part in sorting viral particles during their exit from cells. (Cell Rep. 10, 1496–1507, 2015)