As growing body of evidence suggests that complex signaling pathways are involved in neuronal excitotoxicity and cell loss progress during epilepsy, such as transforming growth factor- (TGF-) β, interleukin- (IL-) 1 receptor/Toll-like receptor (TLR), and cyclooxygenase-2 (COX-2) signaling pathways. This evidence concerns the gene PTGS2 and epilepsy.