Spectrin beta chain, non-erythrocytic 4

SPTBN4 encodes spectrin beta chain, non-erythrocytic 4, a structural protein involved in cytoskeletal organization and cell membrane stability (UniProt: Q9H254). The protein is widely expressed and plays a role in maintaining cellular architecture, particularly in neurons where the spectrin cytoskeleton is essential for axonal integrity and synapse function.

SPTBN4 is associated with neurodevelopmental disorder with hypotonia, neuropathy, and deafness (NEDHND, MIM 617519), an autosomal recessive condition featuring congenital myopathy, progressive muscle atrophy, central deafness, and motor neuropathy (UniProt: Q9H254). This disease relevance underscores the protein's importance in nervous system development and maintenance.

SPTBN4 is downregulated in Alzheimer's disease brain tissue (Chaparral AD proteomics). Analysis of post-mortem AD brain compared to age-matched controls revealed reduced SPTBN4 abundance with a mean log2 fold-change of −0.44 across subcellular fractions, consistent with neurodegeneration-associated cytoskeletal disruption observed in AD pathology.