CHMP2A is a core component of the ESCRT-III complex that mediates membrane remodeling across multiple cellular processes. Primary function involves membrane fission and cytokinetic abscission, where CHMP2A assembles into helical filaments with CHMP3 to constrict and cleave membranes 1. CHMP2A also functions in autophagosome closure, partnering with ATG9A through IQGAP1 to facilitate the final stages of autophagosome biogenesis 2. Mechanistically, CHMP2A exhibits ordered hierarchical assembly with other ESCRT-III isoforms—its depletion causes mislocalization of CHMP4B, CHMP3, and CHMP1B while minimally affecting IST1 and CHMP2B 3. Unlike CHMP2B, CHMP2A requires CHMP3 for membrane binding and induces no significant membrane rigidification 4. Disease relevance includes intellectual disability, where de novo CHMP2A mutations were identified in moderate-to-severe cases 5, and cancer immunotherapy resistance. CHMP2A deletion enhances tumor sensitivity to natural killer cell-mediated cytotoxicity by activating NF-κB signaling and reducing immunosuppressive extracellular vesicle secretion 67. Clinically, CHMP2A inhibition represents a potential strategy to improve NK cell-based immunotherapy outcomes. Additionally, CHMP2A expression is associated with preserved autophagy during cisplatin-induced kidney injury 8.