ADD2 (adducin 2) is a membrane-cytoskeleton-associated protein that functions as a key component of the spectrin-actin cytoskeletal network 1. As a heterodimeric protein encoded by one of three related adducin genes, ADD2 promotes assembly of spectrin-actin networks and provides a link between the spectrin cytoskeleton and plasma membrane through binding to the glucose transporter SLC2A1/GLUT1 2. ADD2 undergoes extensive alternative splicing, producing multiple isoforms (β1, β4a-d) with tissue-specific expression patterns, particularly enriched in brain, liver, and kidney 1. Unlike ADD1, ADD2 exhibits functional nuclear export signals and primarily localizes to the cytoplasm despite possessing a nuclear localization signal, indicating active nuclear-cytoplasmic shuttling 3. Clinically, ADD2 variants are associated with hypertension risk; a specific polymorphism (rs4852706) showed significant association with hypertension in population studies 4. ADD2 expression is regulated by TDP-43, an RNA-binding protein whose depletion reduces ADD2 mRNA stability 5. Since ADD2 participates in synapse assembly and synaptic plasticity, TDP-43-mediated ADD2 loss may contribute to neurodegeneration in ALS and FTD 5. Additionally, serum autoantibodies against ADD2 show diagnostic potential for Alzheimer's disease, where ADD2 is downregulated in affected brain tissue 6.