KDEL (Lys-Asp-Glu-Leu) endoplasmic reticulum protein retention receptor 1, also known as KDELR1, is a protein which in humans is encoded by the KDELR1 gene. Function Retention of resident soluble proteins in the lumen of the endoplasmic reticulum (ER) is achieved in both yeast and animal cells by their continual retrieval from the cis-Golgi or a pre-Golgi compartment. Sorting of these proteins is dependent on a C-terminal tetrapeptide signal, usually lys-asp-glu-leu (KDEL) in animal cells and his-asp-glu-leu (HDEL) in S. cerevisiae. This process is mediated by a receptor that recognizes and binds the tetrapeptide-containing protein and then returns it to the ER. In yeast, the sorting receptor is encoded by a single gene, ERD2, which is a seven-transmembrane protein. Unlike yeast, several human homologs of the ERD2 gene, constituting the KDEL receptor gene family, have been described. The protein encoded by this gene was the first member of the family to be identified, and it encodes a protein structurally and functionally similar to the yeast ERD2 gene product. The KDEL receptor mediates the retrieval of misfolded proteins between the ER and the Golgi apparatus. The KDEL receptor functions by binding to endoplasmic reticulum chaperones. These chaperones are recognized by the KDEL receptor in downstream compartments of the ER. Once bound, they are packaged into coat protein complex I vesicles for retrograde transport to the ER. In vitro studies in yeast have revealed that this receptor regulates membrane transport in the early stages of the secretory pathway from ER to the Golgi. An error or mutation in the KDEL receptor disturbs the ER quality control and diseases associated with ER stress are observed. Dilated cardiomyopathy KDEL receptors have been implicated in the development of dilated cardiomyopathy (DCM). To determine the relationship between KDEL receptor and dilated cardiomyopathy, transgenic mice with a point mutation (D193N) were made. The mice expressing the transport mutant D193N gene grew normally until they reached adulthood. The mutant KDEL receptor did not function after 14 weeks of age, and these mice developed DCM. They were observed to have dilated heart chambers, as well as higher heart-to-body ratios with enlarged hearts, and the cardiac myocytes were larger in size. No difference was observed in arterial blood pressure between wild-type and mutant mice, thus cardiomegaly was not attributed to hypertension. Upon analysis, it was found that KDEL mutant mice had proliferation in their sarcoplasmic reticulum (SR) and a narrowing in