RELN and epilepsy: These observations advance the notion that 320-kDa Reelin fragment protein is a major neuromodulator that (1) increases glutamatergic neurotransmission mediated by the postsynaptic ApoER2 and VLDL receptors and therefore enhances synaptic plasticity, and (2) prevents the suppression of NMDA receptor and LTP in epilepsy patient’s brains and altered expression of Reelin (fragments ratio) and its signal transduction (glycosylation patterns), in part, participate in the initiation of epilepsy.