HCN4 encodes a hyperpolarization-activated cyclic nucleotide-gated ion channel permeable to both Na+ and K+ ions, with preferential selectivity for K+ 1. The channel exhibits very slow activation and inactivation kinetics 123. HCN4 is the primary molecular determinant of the funny current (If) in cardiac sinoatrial node pacemaker cells, where it drives spontaneous depolarization and regulates heartbeat rhythm 145. Beyond the sinoatrial node, HCN4 contributes to pacemaker function in the atrioventricular node and generates hyperpolarization-activated currents (Ih) in neurons 67. HCN4 activity is regulated primarily by cAMP and protein kinase A, enabling neurohumoral modulation of heart rate 6. Pathologically, HCN4 variants associate with multiple arrhythmias: truncating variants and transmembrane mutations link to left ventricular noncompaction with arrhythmogenic phenotypes 8, while the G1097W variant causes atrioventricular block 6. HCN4 downregulation occurs in heart failure and atrial fibrillation, contributing to sinus node remodeling 9. In stem cell therapeutics, HCN4 abolition prevents automaticity in transplanted cardiomyocytes, reducing engraftment arrhythmias 10. HCN4 also plays roles in absence seizure generation 7 and sinoatrial node homeostasis through Hippo signaling interactions 11.