HCN2 encodes a hyperpolarization-activated ion channel permeable to both sodium and potassium ions, with lower selectivity for potassium. It contributes to pacemaker currents in the heart (If) and neurons (Ih), regulating membrane excitability and diastolic depolarization. In the heart, HCN2 dysregulation is implicated in sinus node disease and atrial fibrillation; reduced HCN2 expression occurs in heart failure 1. In the brain, HCN2 dysfunction associates with multiple neurological conditions. Recent evidence demonstrates that HCN2 deficiency correlates with hippocampal pyramidal neuron hyperexcitability and memory impairment in Alzheimer's disease, with reduced HCN2 expression documented in both mouse models and AD patients 2. HCN2 variants cause neurodevelopmental disorders including developmental delay, intellectual disability, epilepsy, and language disorders; functional studies show that pathogenic variants can cause loss-of-function or gain-of-function effects 3. In autism spectrum disorder, HCN2 channelopathy drives thalamocortical circuit dysfunction and sensory hypersensitivity, which can be ameliorated by lamotrigine treatment 4. Additionally, HCN channel blockers show promise for absence seizure treatment 5. These findings identify HCN2 as a critical regulator of neuronal and cardiac excitability with therapeutic potential across multiple disorders.