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The Popeye domain‐containing protein 3 (POPDC3), a transmembrane protein with a unique cyclic adenosine monophosphate (cAMP) binding site, is widely expressed in mammalian tissues, with the highest levels of expression in skeletal muscle. POPDC3 plays a key role in many physiological and pathological processes and is considered a candidate biomarker and potential therapeutic target of cancer. In addition, POPDC3 gene variants have been associated with limb‐girdle muscular dystrophy (LGMD) type 26. However, there are only a few studies on the biological role of POPDC3, interacting proteins, potential downstream targets, and regulated signaling pathways. Therefore, this review focuses on the structure of POPDC3 protein, interacting molecules, and the role and mechanism in cancer, and in cardiac and skeletal muscle, and to review the current research progress of POPDC3 and propose possible future study directions.
POPDC3, a transmembrane protein with a cAMP‐binding site, is down‐regulated in intestinal metaplasia and gastric cancer and gastric cancer and elevated in breast and head and neck squamous cell carcinoma, and is considered a candidate biomarker and a potential therapeutic target of cancer. In addition, POPDC3 variants or homozygous missense lead to LGMD26, and whether it is associated with heart disease needs further confirmation (Created with BioRender.com).