Isoform 2 of Spectrin alpha chain, non-erythrocytic 1

Spectrin alpha chain, non-erythrocytic 1 (SPTAN1) isoform 2 is a large cytoskeletal protein that serves as a structural component of the spectrin-actin network (UniProt: Q13813-2). This 285 kDa protein plays a central role in maintaining cell morphology and organizing membrane-associated structures, with particular importance in neuronal cytoarchitecture. SPTAN1 is widely expressed across tissues including the brain, where it stabilizes axonal and dendritic architecture.

The protein is relevant to neurological function given its essential role in cytoskeletal organization and synaptic integrity. While UniProt records no explicitly curated disease associations for this isoform, the experimental evidence demonstrates altered expression in Alzheimer's disease pathology.

SPTAN1 isoform 2 is downregulated in Alzheimer's disease brain tissue. Post-mortem analysis comparing AD cases to age-matched controls using TMT-labeled quantitative proteomics across four subcellular fractions (P2, P3, S2, S3) revealed a mean log2 fold-change of −0.16, indicating modest but consistent reduction (Chaparral AD proteomics). This downregulation may reflect cytoskeletal disruption or neuronal loss associated with AD neuropathology.