HCN channels, known as hyperpolarization-activated cyclic nucleotide-gated channels, comprise four subtypes: HCN1-4. These channels are tetrameric membrane proteins primarily found in the heart and central nervous system. They open in response to intracellular hyperpolarization, allowing the flow of Na+ and K+ ions, thereby regulating heart rate, neuronal excitability, and rhythmic activities. HCN channels play a crucial role in electrophysiological activity and signal transduction. Gene-specific expression and mutations of HCN channels are associated with conditions such as arrhythmias, epilepsy, and neurodegenerative diseases. Aberrant HCN channel function profoundly affects cellular electrophysiology and disease progression.