KDEL endoplasmic reticulum protein retention receptor 1 (KDELR1)

KDEL endoplasmic reticulum protein retention receptor 1 (KDELR1) is a seven-transmembrane domain receptor responsible for the retrieval and retention of soluble ER-resident proteins carrying the KDEL (Lys-Asp-Glu-Leu) C-terminal motif from the Golgi back to the endoplasmic reticulum[1]. KDELR1 recognizes chaperones and other proteins with a KDEL sequence that inadvertently escape to the Golgi during cellular secretory processes. Upon ligand binding, KDELR1 interacts with heterotrimeric G proteins, Src family kinases, PKA, and MAPKs, thereby orchestrating membrane trafficking flows, Golgi homeostasis, and signaling pathways involved in extracellular matrix remodeling and immune cell development[2][3]. KDELR1-deficient mice and cell models exhibit defects in immune cell populations (notably T lymphocytes), increased ER stress, altered cell adhesion, and increased susceptibility to viral infections[4]. While currently not a direct drug target, KDELR1 is implicated in several pathological states, particularly those involving ER stress, neurodegeneration, cancer progression, and immune function[2][3].

Other names

ER lumen protein-retaining receptor 1ERD2.1KDEL receptor 1ERD2HDEL receptorPutative MAPK-activating protein PM23PM23

Not applicable for approved drugs; mechanistically, targeting KDELR1 could modulate ER stress responses, protein trafficking, and cell adhesion/migration[2].