OSR1 and isolated focal cortical dysplasia type II: Here, using electrophysiology, biochemistry and pharmacological modulation ex vivo in human FCD type II, HMG and TSC, we show physical interactions between mTOR and WNK1/SPAK-OSR1 kinases leading to the phosphorylation of the chloride cotransporters NKCC1/KCC2, resulting in a depolarizing shift of ECl and, ultimately, hyperexcitability and epilepsy.