RPAP3, short for RNA polymerase II-associated protein 3, is a key component of the R2TP co-chaperone complex. The R2TP complex, along with HSP90, is involved in the activation and assembly of multiple macromolecular complexes such as RNA polymerase II and complexes of the phosphatidylinositol-3-kinase-like family of kinases (PIKKs) like mTORC1 and ATR/ATRIP [1]. It also has potential links to the regulation of miRNA activity, ribosome biogenesis, and may play roles in apoptosis and DNA damage response pathways [2,5,6].

The C-terminal domain of RPAP3 is essential for the assembly of R2TP and R2TP-like co-chaperone complexes as it directly interacts with RUVBL2 [1]. In the context of miRNA regulation, RPAP3 binds TRBP, and this binding seems to be involved in sequestering TRBP to regulate the miRNA pathway [2]. One RPAP3-like protein, SPAG1, can form an R2TP-like complex (R2SP) with PIH1D2 and RUVBL1/2, which is required for liprin-α2 expression and complex assembly, suggesting a role in quaternary protein folding [3]. In plants, the Sorghum RPAP3 has functional capabilities similar to its human counterpart, including binding with RUVBLs, Hsp90, and Hsp70, which helps in understanding plant-specific protein assembly [4].

In summary, RPAP3 is crucial for the assembly of R2TP and related complexes, and is involved in multiple biological processes such as macromolecular complex assembly, miRNA regulation, and protein folding. Although no KO/CKO mouse model findings were directly presented in the references, the diverse functions of RPAP3 across different organisms highlight its significance, and further in-vivo studies, potentially including KO/CKO mouse models, could provide more insights into its role in specific disease conditions and biological processes.