PAAF1 (proteasomal ATPase associated factor 1) serves as a multifunctional regulator of proteasome assembly and activity. As a proteasome assembly chaperone, PAAF1 specifically binds to proteasomal ATPases within the 19S regulatory particle and guides proper assembly of the 26S proteasome 1. Paradoxically, PAAF1 also functions as a negative regulator by inhibiting 26S proteasome assembly and preventing stable association of the 19S regulatory complex with the 20S core, thereby reducing overall proteolytic activity 2. PAAF1 plays a critical role in protein quality control by serving as an adaptor that helps the HERC1 ubiquitin ligase identify and eliminate unassembled proteasome intermediates 3. In disease contexts, PAAF1 contributes to HIV-1 transcriptional regulation by promoting proteasome dissociation into 19S and 20S particles, facilitating recruitment of the 19S complex to the viral promoter 4. Additionally, PAAF1 protects the transcriptional elongation factor SUPT6H (Spt6) from proteasomal degradation 5. Dysregulation of PAAF1 has been implicated in Parkinson's disease, where it mediates α-synuclein-induced proteasome dysfunction 6, and homozygous PAAF1 duplications have been associated with rare genetic disease traits 7.