ankyrinB

Ankyrin-B, encoded by the ANK2 gene, is a cytoskeletal adaptor protein that belongs to the ankyrin family. It functions to link integral membrane proteins to the spectrin-based cytoskeleton, helping to organize and stabilize membrane protein complexes. Ankyrin-B contains an ankyrin repeat domain for binding partners, a spectrin-binding domain, and a C-terminal regulatory region. Multiple isoforms are produced by alternative splicing, with tissue-specific expression; the best characterized forms are expressed in brain and heart.

Ankyrin-B is widely expressed in neurons and cardiomyocytes and localizes to the plasma membrane, the transverse tubule network in heart cells, and intracellular membranes. In these cells, it forms complexes with a set of crucial membrane proteins, including the Na+/K+ ATPase, the Na+/Ca2+ exchanger NCX1, and the inositol 1,4,5-trisphosphate receptor (IP3R) on the sarcoplasmic reticulum, among others. It also interacts with cytoskeletal elements such as spectrin and actin, contributing to the organization of membrane domains and trafficking pathways.

Functionally, ankyrin-B acts as a scaffold that coordinates the trafficking, localization, and stabilization of channels and transporters essential for electrical signaling and Ca2+ handling. By maintaining proper localization of these proteins, ankyrin-B supports normal cardiac conduction, Ca2+ homeostasis, and cellular polarity in neurons.

Genetic variations in ANK2 are associated with cardiac conduction disease and arrhythmias, including ankyrin-B syndrome, which reflects disrupted localization of NCX1 and related transporters. In the nervous system, ANK2 variants have been studied for potential links to neurodevelopmental and neuropsychiatric conditions, though findings are preliminary and require further validation.