KDEL receptors (KDELRs) are integral membrane proteins essential for retrieving soluble endoplasmic reticulum chaperones through retrograde transport. KDEL receptors recognize C-terminal ER retention signals (R/H/KDEL) on their cargo and recruit the COPI complex, initiating return of the receptor-chaperone complex to the ER. KDELRs have also recently been shown to play an important role in Golgi/ER homeostasis through non-retrieving signalling pathways, with implications for their use as markers in cancer and inflammatory diseases. However, the molecular mechanisms of KDELR-mediated trafficking and non-trafficking signalling remain unclear. Using a combination of cryo-EM, NMR and in vivo trafficking assays, we demonstrate that KDELRs can exist in monomeric and higher-order forms, potentially hinting at how the activation and downstream signalling of these receptors are regulated. Our results provide further insight into the molecular mechanisms underlying receptor activation and retrograde trafficking mediated by KDEL receptors