Vinculin

Vinculin (VCL) is an actin filament-binding protein that mediates cell-matrix and cell-cell adhesion, regulating E-cadherin surface expression and mechanosensing at cell junctions (UniProt: P18206). It plays important roles in cell morphology and locomotion. While primarily characterized by associations with cardiomyopathies (dilated and hypertrophic forms), vinculin's adhesion functions suggest broader relevance to cellular integrity and communication.

In Alzheimer's disease, vinculin is upregulated in post-mortem human brain tissue compared to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of 0.73 across analyzed subcellular fractions. This upregulation was detected via TMT-labeled quantitative proteomics across multiple subcellular compartments (P2, P3, S2, S3 fractions), suggesting increased vinculin abundance may reflect compensatory responses to synaptic dysfunction or altered cellular adhesion dynamics during neurodegeneration. The functional significance of this elevation in AD pathophysiology remains to be determined.