Based on prior studies revealing that the NF1 protein, neurofibromin, binds to and regulates hyperpolarization-activated cyclic nucleotide-gated (HCN) channels37 and that HCN channels directly modulate neuronal excitability38,39, we now show that HCN channel dysregulation is responsible for Nf1-mutant central and peripheral nervous system neuronal hyperexcitability and consequently increased tumor-driving paracrine factor release, such that HCN channel targeting (using the anti-seizure medication lamotrigine) blocked Nf1-OPG progression in vivo. The gene discussed is NF1; the disease is neoplasm.