CHMP3 is a core component of the ESCRT-III complex, a highly conserved membrane remodeling machinery essential for multiple cellular processes. CHMP3 assembles into helical polymers with other ESCRT-III proteins, particularly CHMP2A, to form tubular structures that constrict and cleave negatively curved membranes 1. This polymer formation is achieved through conformational changes that stabilize individual protomers 2. Mechanistically, CHMP3 selectively binds phosphoinositides (PtdIns(3,5)P2 and PtdIns(3,4)P2) and coordinates with the AAA-ATPase VPS4 to mediate membrane fission events 1. CHMP3 functions in multivesicular body biogenesis and cargo sorting into lysosomes, cytokinesis abscission, and enveloped virus budding, including HIV-1 2. Its activity in endosomal sorting is regulated by CK2α-mediated phosphorylation 3. Disease relevance includes spastic paraplegia: a homozygous CHMP3 missense variant (p.Thr173Ile) causes reduced CHMP3 expression, leading to aberrant autophagy with endosomal and autophagosomal accumulation 4. CHMP3 is also implicated as a biomarker in diabetic foot ulcers, where downregulation correlates with disease progression 5. The functional importance of CHMP3 is underscored by engineered retroCHMP3 variants that potently inhibit viral budding while preserving essential cellular ESCRT functions 6.