Ankyrin-3

Ankyrin-3 (ANK3) is a large membrane-cytoskeleton linker protein that maintains and targets ion channels and cell adhesion molecules at specialized neuronal compartments, including the nodes of Ranvier and axonal initial segments (UniProt: Q12955). It also regulates ion channel activity and promotes localization of cardiac proteins to cell-cell junctions. Beyond its structural roles, ANK3 contributes to intracellular adhesion and junctional conductance in myocytes.

ANK3 is expressed broadly across tissues and has been associated with intellectual developmental disorder, autosomal recessive 37 (MRT37), a neurodevelopmental condition characterized by global developmental delay and neurological symptoms (UniProt: Q12955). Its functions in neuronal organization and ion homeostasis implicate it in brain development and neuronal function.

In Alzheimer's Disease, ANK3 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of −0.749 across subcellular fractions. This reduction may reflect compromised neuronal cytoskeleton integrity or altered ion channel organization in AD pathology, though the functional consequences of this downregulation require further investigation.