In conclusion, three approximations are promising mechanisms in determining the role of KARs in epilepsy: (i) depression of inhibitory synaptic transmission and increase in excitatory transmission (i.e., disruption of excitation/inhibition balance); (ii) induction of reactive plasticity with new KARs changing network properties; and (iii) the emerging role of astrocytes in epilepsy. This evidence concerns the gene KARS1 and epilepsy.