The HMGB1/RAGE/TLR4 signalling pathway is a key player in a number of neurological disorders that do not result in seizures; however, it has been hypothesized that the presence of extracellular HMGB1 contributes to selective vulnerability of neuronal subpopulations (e.g., pyramidal and granule cell neurons) to hyperexcitability and synaptic dysfunction within the inflammatory environment, further augmenting seizure activity [48,51]. The gene discussed is HMGB1; the disease is nervous system disorder.