Isoform 2 of Cytoplasmic dynein 1 intermediate chain 1

Cytoplasmic dynein 1 intermediate chain 1 (DYNC1I1) isoform 2 is a 628-amino acid protein component of the dynein motor complex (UniProt: O14576-2). As an intermediate chain, it facilitates dynein assembly and cargo binding, playing a central role in microtubule-based intracellular transport and organelle positioning.

DYNC1I1 functions within the cytoplasmic dynein pathway, which is essential for neuronal transport processes and cellular homeostasis across multiple tissue types. The protein's role in motor function and vesicle dynamics suggests broad relevance to cellular maintenance pathways.

In Alzheimer's disease, DYNC1I1 isoform 2 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2FC: −0.50; Chaparral AD proteomics). This reduction was detected in a subcellular fractionation study (TMT-labeled quantitative proteomics across P2, P3, S2, and S3 fractions). The downregulation of dynein components may impair axonal transport and contribute to neurodegeneration observed in AD pathology.