HCN2 and generalized epilepsy: This study led to the identification, in a generalized epilepsy patient, of a homozygous recessive mutation located in the C-linker region of HCN2 (E515K; Figure 1A) that determines an almost complete loss of activity of the mutated channel, leading to a significant increase in the activity of neuronal discharge, and of neuronal excitability (DiFrancesco et al., 2011).