The water channel aquaporin 4 (AQP4) is central to the water balance in the brain. AQP4 is mainly found in astrocytes, one of the brain's supporting cells, where it is concentrated in the end-feet of cells surrounding the brain's blood vessels. This is crucial for creating a flow through the brain that helps clear away debris. This flow increases when we sleep and decreases sharply as we age, leading to increased susceptibility to neurodegenerative diseases. AQP4 has therefore been identified as a promising drug target for the development of new treatments for diseases such as Alzheimer's and Parkinson's, but also for brain edema and epilepsy, for example. We have recently characterized how AQP4 is regulated and shown that inhibition of this mechanism by drugs can be used to treat brain edema in rats. This project builds on this important discovery and aims to further our understanding of AQP4 regulation and create protein models that can be used in drug design. To do this, we will study how AQP4 binds to two proteins, calmodulin and alpha-syntrophin, and determine the structure of the protein complexes. We will then use these models to identify potential drug molecules and antibodies that affect the ability to interact. The results will provide crucial information on the role of AQP4 in the brain and provide the opportunity to develop new revolutionary treatment strategies for neurodegenerative diseases.