Receptor expression-enhancing protein 5 (REEP5)

Receptor expression-enhancing protein 5 (REEP5) is an endoplasmic reticulum/sarcoplasmic reticulum membrane-associated protein highly expressed in cardiac and muscle tissue, and also notably present in the brain and some other organs. REEP5 acts as a key regulator of ER/SR structural integrity by generating membrane curvature and stabilizing highly differentiated ER networks, particularly in cardiac myocytes. Loss of REEP5 leads to SR/ER membrane vacuolization, disrupted Ca^2+^ cycling, increased reactive oxygen species (ROS), ER stress, and cardiac dysfunction both in vitro and in vivo. REEP5 also acts as an accessory protein that enhances the function of certain G protein-coupled receptors (GPCRs), notably the chemokine receptor CXCR1, thereby modulating cell proliferation and metastasis in some cancers such as lung and colon cancer. It interacts with other ER-membrane-shaping proteins (e.g., atlastins, reticulons), as well as proteins involved in GPCR regulation. Clinical and preclinical data highlight its essential role in cardiac physiology, as well as a potential pro-oncogenic role in certain tumors. REEP5 may thus serve as a disease marker and potential therapeutic target, but with important safety implications for cardiac function if disrupted.

Other names

C5orf18D5S346DP1TB2YOP1Yip2ereceptor accessory protein 5POB16polyposis locus protein 1deleted in polyposis 1protein TB2polyposis coli region hypothetical protein DP1

For GPCR signaling: enhances proper function and post-endocytosis trafficking of GPCRs such as CXCR1. For cardiac biology: maintains ER/SR architecture, preventing stress response induction, ROS accumulation, and contractile dysfunction.