Spectrin beta chain, non-erythrocytic 2

SPTBN2 encodes spectrin beta chain, non-erythrocytic 2, a large cytoskeletal protein (271 kDa) that plays an important role in the neuronal membrane skeleton (UniProt: O15020). As a non-erythrocytic spectrin, it contributes to the structural organization and stability of neuronal membranes.

SPTBN2 is associated with spinocerebellar ataxias, including the autosomal dominant SCA5 (MIM 600224) and autosomal recessive SCAR14 (MIM 615386), both characterized by progressive cerebellar degeneration and motor dysfunction. These disease associations underscore the protein's critical role in neuronal integrity and function.

In Alzheimer's Disease, SPTBN2 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). The protein showed a mean log2 fold-change of −0.79 across two of four subcellular fractions examined in TMT-labeled quantitative proteomics analysis. This downregulation may reflect cytoskeletal dysfunction and loss of neuronal membrane organization associated with AD pathology.