Isoform B of DnaJ homolog subfamily B member 6

DNAJB6 isoform B is a molecular chaperone from the DnaJ homolog subfamily that functions to inhibit huntingtin aggregation (UniProt: O75190-2). The protein is 241 amino acids in length and belongs to the heat shock protein family, which plays roles in protein quality control and stress response across multiple cellular compartments.

In the context of neurological disease, DNAJB6 has been studied for its anti-aggregation properties, particularly relevant to polyglutamine disorders. The isoform B variant specifically demonstrates inhibitory activity against huntingtin aggregation, distinguishing it functionally from isoform A (UniProt: O75190-2).

DNAJB6 isoform B is significantly upregulated in Alzheimer's disease brain tissue. Analysis of post-mortem AD brain compared to age-matched controls using TMT-labeled proteomics across four subcellular fractions (P2, P3, S2, S3) revealed an upregulation with a mean log2 fold-change of 0.67 (Chaparral AD proteomics). This elevated expression may reflect a compensatory response to protein aggregation and misfolding processes characteristic of AD pathology.