Charged multivesicular body protein 3

Charged multivesicular body protein 3 (CHMP3) is a core component of the ESCRT-III complex involved in multivesicular body (MVB) formation and endosomal cargo sorting (UniProt: Q9Y3E7). The protein mediates vesicle invagination and membrane scission events, facilitating the delivery of cargo to lysosomes for degradation. CHMP3 also participates in cytokinesis and enveloped virus budding, and selectively binds phosphoinositides to regulate these trafficking processes.

CHMP3 functions in endosomal-lysosomal pathways critical for protein quality control and cellular housekeeping. It plays a role in EGF receptor trafficking and stress response mechanisms, with isoform 2 conferring cytoprotection against oxidative damage in cellular models.

In Alzheimer's disease, CHMP3 is significantly downregulated in post-mortem AD brain compared to age-matched controls (mean log2FC −0.417; Chaparral AD proteomics). This reduction may reflect impaired endosomal-lysosomal degradation capacity in AD, a pathway implicated in the accumulation of neurotoxic proteins including amyloid-β and tau.