Fig. 3. Structure of the human LRRC8 channel (PDB 5ZSU) [66]. The monomer (left) can be divided into four structural domains: the extracellular domain (ECD), the transmembrane domain (TMD), the intracellular linker domain (ILD), and the leucine-rich repeat domain (LRRD). The functional LRRC8 channel shows a hexameric structure (middle) and is formed by LRRC8A subunits and at least one other LRRC8 isoform (LRRC8B-LRRC8E). The hexameric structure displays a 6-fold symmetry on the level of the TMD and a 3-fold symmetry on the level of the LRRD (right). Consequently, the cytosolic domain exhibits the structure of a trimer of dimers.