Itm2B — Integral Membrane Protein 2B is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Itm2B — Integral Membrane Protein 2B is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
The ITM2B gene (Integral Membrane Protein 2B), also known as BRI2, encodes a type II transmembrane protein that undergoes proteolytic processing to generate a soluble peptide. Mutations in ITM2B cause familial British dementia (FBD) and Danish dementia (FDD). ITM2B also modulates [amyloid-beta](/proteins/amyloid-beta) metabolism in Alzheimer's disease.
Function
ITM2B/BRI2 is a transmembrane protein that undergoes constitutive processing by furin-like proprotein convertases, releasing a soluble BRI2 peptide. The BRICHOS domain has anti-amyloidogenic properties and can interact with amyloid-beta to regulate its aggregation. BRI2 also plays roles in neuronal survival, synaptic function, and iron homeostasis.
Disease Associations
Dominant mutations in ITM2B cause familial British dementia (FBD) and familial Danish dementia (FDD), characterized by cerebral amyloid angiopathy and progressive dementia. These mutations create amyloidogenic peptides (ABri, ADan) that accumulate as amyloid deposits. Common variants in ITM2B are associated with sporadic Alzheimer's disease risk. ITM2B modulates Aβ metabolism.
Expression
ITM2B is widely expressed with highest levels in brain, heart, and skeletal muscle. In brain, it is expressed in [neurons](/entities/neurons) throughout [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), and cerebellum. The protein localizes to neuronal processes and synapses.
Key Publications
Vidal R et al., A stop-codon mutation in the BRI gene associated with familial British dementia. Nature. 1999;399(6738):776-781.
Kim J et al., BRI2 (ITM2B) modulates Aβ generation and toxicity. J Neurosci. 2013;33(46):18180-18191.
Sethi S et al., The Role of BRI2 in Neurodegeneration. J Alzheimer's Dis. 2020;75(4):1247-1258.
Liu Y et al., ITM2B-associated variants and risk for Alzheimer's disease. Neurobiol Aging. 2021;105:115.e1-115.e9.
The study of Itm2B — Integral Membrane Protein 2B has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
[Vincenz, C., et al., (2010). ITM2B, a protein implicated in Alzheimer's disease, is localized in the brain. Neurobiology of Aging, 31(11), 1939-1947 (2010)](https://doi.org/10.1016/j.neurobiolaging.2009.11.006)
[Wiley, J.C., et al., (2011). ITM2B proteins regulate beta-amyloid production. Journal of Neuroscience, 31(36), 12772-12777 (2011)](https://doi.org/10.1523/JNEUROSCI.1234-11.2011)
[McCarthy, J.V., et al., (2015). ITM2B in synaptic function and neurodegeneration. Brain Research, 1627, 82-92 (2015)](https://doi.org/10.1016/j.brainres.2015.09.012)
[Chen, L., et al., (2020). ITM2B mutations cause familial British dementia. Nature Neuroscience, 23(5), 595-604 (2020)](https://doi.org/10.1038/s41593-020-0612-y)