POPDC1 is a cAMP-binding protein with critical roles in cardiac and skeletal muscle function and cell adhesion. In the heart, POPDC1 regulates cardiac pacemaking and conduction through cAMP signaling compartmentalization, with mutations causing atrioventricular block exacerbated by sympathetic nervous system activation 1. The protein functions as a plasma membrane-localized effector that modulates cardiac electrophysiology and intracellular calcium handling 1. POPDC1 also serves as a cell adhesion molecule maintaining epithelial tight junction integrity and regulating receptor recycling through interactions with VAMP3 and Rho-family GTPases. Disease relevance centers on inherited muscle disorders and cardiac arrhythmias. A homozygous S201F missense mutation causes limb-girdle muscular dystrophy and cardiac arrhythmia through impaired protein trafficking and reduced cAMP affinity 2. Additionally, POPDC1 acts as a tumor suppressor in multiple cancers. In breast cancer, POPDC1 suppression promotes cell migration and proliferation via EGFR-mediated regulation, with cAMP interaction upregulating POPDC1 expression 34. Similar suppression occurs in colon cancer, where CaM antagonists upregulate POPDC1 to inhibit cancer cell growth 5. Therapeutically, restoring POPDC1 expression represents a potential strategy for both cardiac arrhythmia management and cancer treatment.