RPAP3 (RNA polymerase II associated protein 3) functions as a central adapter protein within the R2TP/PAQosome co-chaperone complex, which works with HSP90 to facilitate assembly and stabilization of diverse macromolecular complexes 1. RPAP3 contains a conserved C-terminal domain that directly binds RUVBL1/RUVBL2 AAA+ ATPases, which is essential for R2TP complex formation and is found in all R2TP and R2TP-like complexes 2. The protein spans both faces of a single RUVBL ring, providing an extended flexible scaffold that recruits client proteins and tethers HSP90 to facilitate their assembly 3. RPAP3 recruits specific clients through its TPR domains and collaborates with PIH1D1 to direct substrate recognition and positioning 4. Beyond its canonical role in RNA polymerase II assembly, RPAP3 participates in assembly of phosphatidylinositol-3-kinase-like kinase (PIKK) complexes including mTORC1 and ATR/ATRIP 2, and directly interacts with TSC2 to support TSC complex assembly, a key regulator of mTORC1 5. Emerging evidence implicates RPAP3 in ciliogenesis, RNA silencing, DNA damage response, and metabolic regulation 1. The RPAP3 C-terminal domain is conserved across species and serves as an identifying feature of R2TP-like complexes with specialized functions 6, highlighting its fundamental importance in quaternary protein assembly mechanisms.