Ankyrins and neurological disease.

Ankyrins are scaffolding proteins widely expressed throughout the nervous system. Ankyrins recruit diverse membrane proteins, including ion channels and cell adhesion molecules, into specialized subcellular membrane domains. These domains are stabilized by ankyrins interacting with the spectrin cytoskeleton. Ankyrin genes are highly associated with a number of neurological disorders, including Alzheimer's disease, schizophrenia, autism spectrum disorders, and bipolar disorder. Here, we discuss ankyrin function and their role in neurological disease. We propose mutations in ankyrins contribute to disease through two primary mechanisms: 1) altered neuronal excitability by disrupting ion channel clustering at key excitable domains, and 2) altered neuronal connectivity via impaired stabilization of membrane proteins.