Fermitin family member 2 (FERMT2) (FERMT2)

Fermitin family member 2 (FERMT2), widely known as Kindlin-2, is a multi-domain scaffolding protein essential for the regulation of integrin-mediated cell adhesion and signaling [1, 4]. It primarily functions by binding to the cytoplasmic tail of beta-integrin subunits, working in concert with talin to trigger the "inside-out" activation of integrins, which is crucial for cell-matrix interactions [1, 2]. Beyond its role at focal adhesions, FERMT2 can translocate to the nucleus where it acts as a co-activator for various transcription factors, influencing pathways such as TGF-beta, Wnt/beta-catenin, and Hedgehog signaling [2]. In oncology, FERMT2 is frequently upregulated and serves as a driver of the epithelial-mesenchymal transition (EMT), promoting tumor invasion, metastasis, and chemoresistance in cancers such as breast, prostate, and pancreatic carcinoma [2]. Furthermore, FERMT2 has been identified as a significant genetic risk factor for Alzheimer's disease, where it interacts with the amyloid precursor protein (APP) to modulate its processing and the subsequent production of amyloid-beta peptides [3]. While no FDA-approved drugs currently target FERMT2, its pivotal role in both cancer progression and neurodegeneration makes it a high-priority candidate for the development of novel therapeutic inhibitors and stabilizers [2, 3]. References: [1] UniProt (Q96AC1); [2] Zhan et al. (2019) PMID: 31110054; [3] Eysert et al. (2019) PMID: 30643246; [4] NCBI Gene (10979).

Other names

Kindlin-2PLEKHC1MIG-2UNC112BPleckstrin homology domain-containing family C member 1Mitogen-inducible gene 2 protein

Binding to the cytoplasmic tail of beta-integrins to facilitate conformational changes and activation; scaffolding of signaling proteins to modulate TGF-beta and Wnt pathways.