[7] In the CNS, AQP4 is the most prevalent aquaporin channel, specifically located at the perimicrovessel astrocyte foot processes, glia limitans, and ependyma.

[12] Within the retina, AQP4 is highly concentrated where the processes of Müller cells have a basal lamina around blood vessels and inner limiting membrane[10] and to a lesser degree in the inner and outer plexiform layers.

[15] Specifically within the central nervous system (CNS), AQP4 can be found along the spinal cord and serves as the main water channel.

[18] Aquaporin-4's overall function is to provide fast water transportation as well as maintain homeostatic balance within the central nervous system.

Within the inner ear, the main role is to provide osmotic balance in supporting epithelium cells within the organ of Corti by recycling K+.

[16] Other performances that aquaporin-4 is involved in are synaptic plasticity, astrocyte migration, regulation of extracellular space volume, and the homeostasis of potassium.

[16] The condition known as neuromyelitis optica, NMO, is a rare demyelinating, inflammatory disorder of the CNS that primarily affects the optic nerves and spinal cord of individuals.

[20] Aquaporin-4 is the predominant autoimmune target in 2/3 neuromyelitis optica and higher AQP4 autoantibody levels are associated with the occurrence of optic neuritis (ON),[21] however serum AQP4-IgG titer only moderately reflects disease activity, severity, or neurological prognosis.

[8] Other clinical significant implications of AQP4 in the human body is the role in the regulation of cerebrospinal fluid (CSF) in the ventricles.

With further research into the role of AQP4, it may be possible to modify the human body's system of upregulation of these channels to help in the reabsorption of CSF without the need to use physically invasive treatments.

[16] In rodent models, AQP4 appears plays a role in both the development and resolution of the cerebral edema that occurs following an injury like TBI or stroke and around brain tumors.

When there is an decrease in AQP4, CAA severity increases and vice versa; it is not known what causes changes in AQP4 expression levels, nor whether this is part of the disease process or an effort of the brain to adapt.

[16] In animal models of amyotrophic lateral sclerosis, AQP4 is overexpressed in the brainstem, cortex, and gray matter of the spinal cord which results in swollen astrocytes; the reason for this is not understood.