Charged multivesicular body protein 4a

CHMP4A (Charged multivesicular body protein 4a) is a core component of the ESCRT-III complex involved in multivesicular body (MVB) formation and endosomal cargo sorting (UniProt: Q9BY43). It mediates the invagination and scission of intraluminal vesicles within endosomes, directing cargo toward lysosomal degradation. The protein also participates in cytokinesis and the budding of enveloped viruses, and facilitates exosomal release of cargo proteins including SDCBP and CD63.

CHMP4A functions within the broader ESCRT machinery that coordinates sequential membrane remodeling across multiple cellular compartments. Its role in MVB-dependent degradation pathways positions it within vesicular trafficking and endolysosomal homeostasis networks essential for cellular protein quality control.

CHMP4A is down-regulated in Alzheimer's Disease brain tissue (Chaparral AD proteomics). Post-mortem human AD brain showed reduced CHMP4A levels compared to age-matched controls (mean log2 fold-change: −0.76), based on TMT-labeled quantitative proteomics across four subcellular fractions. This reduction may reflect compromised endosomal-lysosomal function, a pathway increasingly implicated in AD pathogenesis.