Silbernagel et al. (2018) reported that HCN2 and VAPB were co-localized in both HCN2-transfected HeLa cells and VAPB-transfected HeLa cells. However, this co-localization was not observed in HeLa cells transfected with the VAPBP56S mutant (Silbernagel et al., 2018). Indeed, HCN2 current amplitude was noticeably decreased by VAPB modulation. Mutation or loss of VAPB led to a decrease in HCN activity and neuronal excitability in motor neurons, which are a main cell type involved in the pathogenesis of ALS (Silbernagel et al., 2018). Here, HCN2 is linked to amyotrophic lateral sclerosis.