In this study, we employed weighted gene co‐expression network analysis (WGCNA) to identify the basic helix‐loop‐helix (bHLH) family member e41 (BHLHE41, also known as DEC2) as a critical regulator of intrinsic and synaptic neuronal plasticity in temporal lobe epilepsy (TLE). Here, BHLHE41 is linked to temporal lobe epilepsy.