ENY2 is an evolutionarily conserved multifunctional protein and is a member of several complexes that regulate various stages of gene expression. ENY2 is a subunit of the TREX-2 complex, which is necessary for the export of bulk mRNA from the nucleus to the cytoplasm through the nuclear pores in many eukaryotes. The wide range of ENY2 functions suggests that it can also associate with other protein factors or complexes. In a search for proteins that interact with ENY2 of Drosophila melanogaster, a cDNA library was screened in a yeast two-hybrid system. ENY2 was thus found to interact with the RNA-binding protein Paip2. Paip2 directly bound ENY2 in vitro and interacted with ENY2 in vivo at the molecular and genetic levels. Paip2 was capable of association with the ENY2-containing TREX-2 complex. Paip2 was present at the locus of the histone gene cluster. Both Paip2 and ENY2 were detected at histone locus body (HLBs), nuclear structure where coordinated histone mRNA transcription and processing take place. Paip2 and subunits of the TREX-2 complex were shown to associate with histone mRNP particles. A Paip2 knockdown via RNA interference resulted in decreased binding of TREX-2 subunits to histone mRNPs. Thus, Paip2 was identified as a new partner protein of ENY2 within the TREX-2 complex and suggested to participate in TREX-2 binding to histone mRNPs.