Fermitin family homolog 2

Fermitin family homolog 2 (FERMT2) is a scaffolding protein that enhances integrin activation through interaction with talin proteins (TLN1/TLN2) and phosphoinositide-enriched membranes (UniProt: Q96AC1). The protein plays critical roles in focal adhesion assembly, integrin-mediated cell adhesion, and actin cytoskeleton organization. FERMT2 also participates in Wnt and TGF-β signaling by stabilizing β-catenin (CTNNB1) and regulating its transcriptional activity with TCF4, connecting extracellular matrix adhesion to intracellular signaling cascades (UniProt: Q96AC1).

FERMT2 functions across tissues where integrin signaling and cell-matrix interactions are essential, including the central nervous system. No primary disease associations are annotated in UniProt for this protein.

FERMT2 is elevated in Alzheimer's disease brain tissue relative to age-matched controls (Chaparral AD proteomics). Quantitative analysis from human post-mortem AD brain using TMT-labeled mass spectrometry across subcellular fractions revealed a mean log2 fold-change of +0.23, indicating modest upregulation in AD neuropathology. This dysregulation may relate to alterations in cytoskeletal dynamics, focal adhesion turnover, or Wnt signaling perturbations characteristic of AD pathogenesis.