Aqp4, short for Aquaporin4, is a water channel protein mainly expressed in the central nervous system, especially in the foot processes of astrocytes, surrounding capillaries, beneath pia matter, and lining the ventricles. It plays a crucial role in brain water homeostasis and is involved in the "glymphatic system", a concept proposed in 2012, where it may help in the continuous interchange between cerebrospinal fluid and brain interstitial fluid, facilitating waste clearance from the CNS [1,2].

In preclinical AQP4 wild-type and knockout (KO) studies related to depression, stress or inflammation decreased AQP4 protein and gene expression in various brain regions in wild-type models. In KO studies, AQP4 expression was necessary to prevent stress-and inflammation-induced reduced neurogenesis, gliogenesis, increased apoptosis, and depressive-like behaviors [5]. Also, in the context of proteinopathies such as Alzheimer's disease, an extended form of AQP4 has been shown to increase amyloid-β (Aβ) clearance from the brain, suggesting its potential as a therapeutic target [2]. Pathogenic antibodies targeting AQP4 are associated with Neuromyelitis optica spectrum disorder (NMOSD), a severe relapsing remitting demyelinating disease [3,4,6]. AQP4 expression has also been associated with glioma malignancies, though the exact mechanisms of its translocation and impact on glioma progression need further study [7].

In conclusion, Aqp4 is essential for brain water balance and waste clearance. Model-based research, especially KO studies, has revealed its significance in diseases like depression, Alzheimer's, NMOSD, and glioma. Understanding Aqp4's functions through these models provides insights into disease mechanisms and potential therapeutic strategies for these neurological conditions.