Epilepsy is a complex neurological disorder characterized by recurrent seizures, caused by abnormal electrical activity in the brain. At the cellular level, this dysregulation results from an imbalance in ion flux across the neuronal membrane, a process tightly regulated by ion channels. These channels control the movement of ions such as sodium (Na⁺), potassium (K⁺), calcium (Ca²⁺), and chloride (Cl⁻), which are essential for maintaining neuronal excitability and synaptic transmission. Mutations in the genes encoding these channels can disrupt this balance, leading to excessive neuronal excitability and the onset of seizures. Disorders caused by mutations in ion channel genes are known as channelopathies.

Channelopathies in epilepsy involve numerous genes, and the same mutation can lead to different clinical phenotypes. Additionally, there are other genes and environmental factors that can influence the severity of the disease. Some channelopathies respond particularly well to specific anti-seizure medications (ASMs), while other ASMs may be ineffective or even worsen epileptic seizures. This makes diagnosis difficult and delays therapeutic intervention. Identifying new mutations responsible for channelopathies and better understanding the role of ion channels in the pathophysiological mechanisms of epilepsy are challenging yet crucial objectives, essential for improving patients' quality of life. A multidisciplinary approach is necessary for managing these disorders.

The aim of this Research Topic is to gather the latest advancements in the field of channelopathies associated with epilepsy. Key areas of interest include, but are not limited to:

• The study of the role of epigenetic modulation in the regulation of ion channels;
• The investigation of the gut microbiome's influence on ion channels and epileptic activity;
• Innovations in gene therapy and RNA-based therapies;
• The development of advanced humanized models such as brain organoids;
• Progress in electrophysiology and artificial intelligence;
• And the integration of big data with multi-omics approaches.

These advancements could accelerate the functional characterization of each mutation, enhance the understanding of the pathophysiology of channelopathies in epilepsy, and contribute to the optimization of precision medicine.

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Emerging Strategies for Channelopathies in Epilepsy