<p>Temporal lobe epilepsy (TLE) is the most common type of focal epilepsy in adults that resists the conventional anti-seizure medications (ASMs). The spontaneous epileptic seizures in TLE are initiated within one or both temporal lobes, resulting in memory impairment, mood disorders, and learning defects, and may induce the development of secondary generalized epilepsy. Furthermore, a brain water channel, aquaporin 4 (AQP4), is highly dysregulated in epilepsy. AQP4 is intricate in the regulation of neuronal excitability and the development of epileptogenesis and epilepsy. It has been shown that upregulation and mislocalization of AQP4 in the hippocampus and frontal cortex are associated with the development of post-traumatic epilepsy. Additionally, overexpression of AQP4 in certain brain regions is linked with the development of epilepsy. Contrariwise, AQP4 expression in the hippocampus and piriform cortex is deregulated following status epilepticus (SE). Likewise, a reduction of AQP4 expression is associated with the frequency and the severity of epileptic seizures in animal models. These findings highlighted that AQP4 has a dual role, either protective or detrimental, in the pathogenesis of TLE. Therefore, this review aims to discuss the beneficial and detrimental role of AQP4 in TLE.</p> Graphical Abstract <p></p>