The brain is a highly energy-dependent organ. At rest, it requires approximately 20% of oxygen and 25% of glucose relative to the rest of the body, although the brain comprises only 2–3% of total body weight. Neurons have an exceedingly high energy demand due to many cellular housekeeping functions such as synthesis and degradation of macromolecules, maintenance of cytoskeletal dynamics and axoplasmic transport, as well as other costly bioenergetic functions related to the high level of action potential signaling, synaptic activity, and plasticity changes. Lactate cannot passively diffuse across the blood brain barrier30, and since it cannot be directly utilized for energy production, it must be first transported via monocarboxylic transporters (MCTs) into cells, and then be subsequently converted enzymatically to pyruvate by lactate dehydrogenase (LDH) which exists in multiple isoforms – LDH1 being primarily expressed in neurons and LDH5 in astrocytes. However, the ANLS hypothesis is not without some controversy, as there is evidence that oxidative metabolism of lactate in neurons may not always be important for synaptic neurotransmission and the directionalities of lactate transport under different physiological conditions remain unclear. To truly appreciate the crucial role of metabolism in epilepsy and its pathophysiology, it is important to acknowledge the existence of bi- and multi-directional molecular interactions, which add layers of complexity to the many vicious cycles implicated thus far in the processes of epileptogenesis.