| Property | Value |
|---|---|
| Protein Name | Bridging Integrator 1 (BIN1) |
| Gene | BIN1 |
| UniProt ID | O00499 |
| Molecular Weight | ~65-70 kDa (isoform dependent) |
| Subcellular Localization | Plasma membrane, T-tubules, endocytic vesicles |
| Protein Family | BAR domain proteins (Amphiphysin family) |
| Diseases | Alzheimer's Disease, Myotonic Dystrophy, Cardiomyopathy |
BIN1 (Bridging Integrator 1) is a BAR domain protein encoded by the BIN1 gene that plays critical roles in membrane remodeling, endocytosis, and intracellular trafficking[1][2]. It has emerged as the second most significant genetic risk factor for late-onset Alzheimer's disease after APOE, with robust associations with tau pathology and disease progression[3][4].
BIN1 is a member of the BAR (Bin/Amphiphysin/Rvs) domain protein family with a modular architecture[5]:
BIN1 has over 10 alternatively spliced isoforms:
BIN1 is essential for membrane remodeling[6]:
BIN1 participates in vesicle trafficking:
BIN1 modulates autophagic processes:
GWAS have identified BIN1 as a major AD risk locus[3:1][7]:
BIN1 is uniquely associated with tau pathology[4:1][8]:
BIN1 connects amyloid and tau pathologies:
BIN1 modulates immune responses:
Therapeutic strategies are being explored[9]:
BIN1-based therapies may combine with:
Chapman, J. et al. BIN1 modulates tau pathology in Alzheimer's disease. Nature Neuroscience. 2013. ↩︎
De Rossi, P. et al. BIN1 regulates tau pathology in vivo. Neuron. 2020. ↩︎
Lambert, J.C. et al. Meta-analysis of genome-wide association studies in AD. Nature Genetics. 2013. ↩︎ ↩︎
Franzmeier, N. et al. BIN1 induces Tau-dependent network hyperexcitability. Brain. 2020. ↩︎ ↩︎
Takano, T. & Zigmond, M.J. BIN1 structure and function. Trends in Neurosciences. 2020. ↩︎
Pant, S. et al. BAR domain proteins and membrane curvature. Trends in Cell Biology. 2012. ↩︎
Hu, X. et al. BIN1 genetic variants and AD risk. Nature Communications. 2019. ↩︎
Busche, M.A. et al. Increased expression of BIN1 mediates AD genetic risk. Nature Neuroscience. 2019. ↩︎
Lasagna-Reeves, C.A. et al. BIN1 in Alzheimer's disease. Journal of Alzheimer's Disease. 2023. ↩︎