ADD2

ADD2, or beta-adducin, is a human gene that encodes a member of the adducin family of cytoskeletal proteins. Adducins are cytoskeletal adaptors that regulate the assembly of the spectrin–actin network underlying the plasma membrane. The ADD2 gene product forms heteromeric complexes with the alpha- and gamma-adducin subunits (encoded by ADD1 and ADD3) to create heterotetramers that cap and recruit actin filaments to spectrin-based networks. Beta-adducin is expressed in erythrocytes and various tissues, and it participates in stabilizing the plasma membrane and maintaining cell shape. In erythrocytes, adducins contribute to membrane stability and deformability; in non-erythroid cells they may influence cell adhesion, polarity, and migration.

Phosphorylation by protein kinases such as protein kinase C modulates adducin activity, influencing its association with spectrin and actin and thereby regulating the cytoskeletal network. The protein can also be regulated by calcium/calmodulin in some contexts, which can affect its binding properties and assembly dynamics.

Genetic studies have explored ADD2 variants in relation to cardiovascular and metabolic traits, including blood pressure regulation. However, associations are not consistently replicated, and no disease-causing ADD2 mutations have been definitively established in the general population. Overall, ADD2 is characterized as a component of the membrane-associated cytoskeleton, contributing to cell shape maintenance and membrane stability across multiple tissues.