Summary: CHMP4B

CHMP4B (charged multivesicular body protein 4b) is a core component of the ESCRT-III complex, a protein machinery essential for multivesicular body formation and endosomal cargo sorting (UniProt: Q9H444). The protein mediates vesicle invagination and membrane fission events, facilitating the delivery of cargo-containing intraluminal vesicles to lysosomes for degradation. CHMP4B also participates in cytokinesis, nuclear envelope sealing, and exosomal cargo release.

The ESCRT-III pathway operates across multiple cellular compartments involved in membrane trafficking and protein quality control. UniProt lists CHMP4B mutations in association with cataract formation (CTRCT31, MIM 605387), reflecting its broader roles in cellular membrane dynamics.

CHMP4B is significantly downregulated in post-mortem Alzheimer's disease brain tissue relative to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of −0.93 across analyzed subcellular fractions. This downregulation may impair endosomal-lysosomal cargo processing and protein clearance pathways, processes increasingly recognized as dysregulated in AD pathogenesis.