Charged multivesicular body protein 5 (CHMP5)

Charged multivesicular body protein 5 (CHMP5) is a coiled-coil protein and a core component of the ESCRT-III endosomal sorting complex required for the proper trafficking and lysosomal degradation of internalized membrane proteins, thus regulating downregulation of activated cell surface receptors such as TGFβ and EGFR[1][2]. CHMP5 is essential for late endosomal function, promoting the maturation of multivesicular bodies (MVBs) and their fusion with lysosomes; its deficiency results in impaired lysosomal degradation, enlarged late endosomes, dysregulated signaling, and can provoke cell senescence and abnormal bone formation[1][2]. In certain cancers, notably T cell acute lymphoblastic leukemia (T-ALL), CHMP5 has a context-specific role in the nucleus, recruiting epigenetic regulators (BRD4, p300) to oncogenic super-enhancers, establishing a key link between vesicular trafficking and transcriptional regulation[3]. CHMP5 also interacts with and regulates the cell surface turnover of T cell receptors, implicating it in immune homeostasis[5]. As a result, CHMP5 is a multifunctional protein whose dysfunction is associated with developmental, immune, musculoskeletal, and neoplastic diseases[1][2][3][5].

Other names

VPS60Vps60C9orf83SNF7DC2CGI-34HSPC177PNAS-2Chromatin-modifying protein 5SNF7 domain-containing protein 2Vacuolar protein sorting-associated protein 60small protein with inherent killing effectSpike

Modulation of receptor degradation and signal transduction through ESCRT-III-mediated endosome-to-lysosome trafficking[1][2] In leukemia, recruitment of chromatin regulators (e.g., BRD4, p300) to enhancers associated with key oncogenic genes[3]