HCN1 encodes a hyperpolarization-activated, cyclic nucleotide-gated ion channel that is permeable to both sodium and potassium ions, displaying lower selectivity for K+ over Na+ 1. The channel generates pacemaker currents (Ih) that control neuronal excitability and contribute to cardiac pacemaker activity 1. HCN1 is predominantly expressed in neocortical and hippocampal neurons and functions through voltage-dependent gating mechanisms that can be modulated by propofol binding to a conserved methionine-phenylalanine interface 2. The channel plays critical roles in dissociative states, with local HCN1 pacemakers in retrosplenial cortex required for ketamine-induced dissociation-like effects 3. Pathogenic HCN1 variants cause a spectrum of epileptic disorders, from severe developmental epileptic encephalopathy to milder generalized epilepsies 14. De novo mutations in transmembrane domains typically cause severe phenotypes through cation leak mechanisms, while variants outside these domains associate with milder phenotypes 1. Decreased HCN1 expression is observed in epilepsy models and patients, creating a paradoxical relationship where reduced HCN1 increases neuronal excitability yet HCN channel blockers can have antiepileptic effects 5. The channel shows sex-specific expression differences in motor neurons and represents a potential therapeutic target for precision epilepsy treatments 64.