Drug resistance is one of the most serious issues in epilepsy.Despite using various appropriate anti-epileptic drugs (AEDs),30％ of epilepsy patients are still drugresistant.The percentage of resistance in temporal lobe epilepsy (TLE) is even higher [1].Although epilepsy surgery and deep brain stimulation are emerging as alternative therapeutic strategies,the curative outcome is still unsatisfactory.So far,the precise mechanisms of drug resistance are still “tales from the mist”,which restricts the discovery of optimal targets and the further application of precise treatment.A recent study by Xu et al.[2] first revealed the critical “gating” role of subicular pyramidal neurons in drug-resistant TLE and unveiled the genesis of drug resistance in TLE at the neuronal level.