KDEL endoplasmic reticulum lumen protein retaining receptor (KDELR)

The KDEL receptor (KDELR) is a seven-transmembrane protein that plays a critical role in maintaining endoplasmic reticulum (ER) proteostasis by retrieving escaped ER-resident proteins from the Golgi apparatus (UniProt, P24555). It specifically recognizes the C-terminal Lys-Asp-Glu-Leu (KDEL) motif or related sequences on proteins, facilitating their retrograde transport via COPI-coated vesicles (PubMed, 29432131). Recent research has identified the KDEL receptor as a signaling molecule that activates G-protein-mediated pathways, such as Gs and Gq, to regulate Golgi-to-ER trafficking and the unfolded protein response (PubMed, 20813264). In oncology, KDELR expression is often upregulated and correlates with increased metastatic potential and poor prognosis in various cancers (PubMed, 31515468). Furthermore, the receptor is exploited by certain bacterial and plant toxins, such as Cholera toxin and Ricin, to gain entry into the ER (PubMed, 11060024). While not a traditional target for small molecule drugs, it is being explored as a mechanism for the targeted delivery of therapeutic proteins and as a potential target for modulating secretory flux in disease states (PubMed, 33483478).

Other names

ERD2ERD2.1ERD2.2ERD2.3KDEL receptor 1KDEL receptor 2KDEL receptor 3

Binding of KDEL-motif containing proteins in the Golgi apparatus followed by retrograde transport to the endoplasmic reticulum via COPI-coated vesicles (PubMed, 29432131).