HCN2 encodes a hyperpolarization-activated ion channel permeable to both sodium and potassium ions with lower K+ selectivity 12. The channel generates pacemaker currents (If) in cardiac tissue and (Ih) in neurons, contributing to spontaneous activity generation and heart rate control 134. HCN2 regulates neuronal excitability, dendritic integration, and membrane potential 4. Pathogenic variants in HCN2 cause neurodevelopmental disorders including developmental delay/intellectual disability (17/21 patients), epilepsy (10/21), language disorders (16/21), and movement disorders (12/21) 5. Functional analyses reveal variants can cause loss-of-function through impaired membrane trafficking or gain-of-function through increased conductance 5. HCN2 dysregulation also associates with Alzheimer's disease; reduced HCN2 expression in hippocampal CA1 pyramidal neurons correlates with neuronal hyperexcitability and memory deficits in both mouse models and AD patients, while HCN2 overexpression rescues these phenotypes 6. Additionally, HCN2 variants link to familial febrile seizures and idiopathic generalized epilepsy 17 7. HCN2 shows dysregulation in schizophrenia-associated genetic risk in orbitofrontal cortex excitatory neurons 8.