CHMP2B is a component of the ESCRT-III complex, which plays a critical role in membrane remodeling and the regulation of endosomal trafficking, particularly in the degradation of endosomes into lysosomes. It is associated with the cytoskeleton in neurons and is thought to strengthen dendritic spines. Mutations in the CHMP2B gene are linked to autosomal dominant frontal temporal dementia (FTD) in humans, and are associated with the death of cortical neurons due to dendritic retraction and the accumulation of ubiquitinated proteins and autophagosomes. CHMP2B also has a role in regulating TDP-43 phosphorylation and cytotoxicity independent of autophagy via the protein kinase CK1. Furthermore, CHMP2B's function in the autophagy pathway and its impact on TDP-43 phosphorylation can independently contribute to cell toxicity and neurodegeneration. The protein's role in membrane remodeling is highlighted by its ability to form a protein network on the membrane surface, enhancing membrane rigidity, which is important for understanding the mechanics of membrane remodeling and scission.
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