In metazoans, nuclear export of bulk mRNA is mediated by Tap-p15, a conserved heterodimeric export receptor that cooperates with adaptor RNA-binding proteins. In this article, we show that Thoc5, a subunit of the mammalian TREX complex, binds to a distinct surface on the middle (Ntf2-like) domain of Tap. Notably, adaptor protein Aly and Thoc5 can simultaneously bind to non-overlapping binding sites on Tap-p15. In vivo, Thoc5 was not required for bulk mRNA export. However, nuclear export of HSP70 mRNA depends on both Thoc5 and Aly. Consistent with a function as a specific export adaptor, Thoc5 exhibits in vitro RNA-binding activity and is associated with HSP70 mRNPs in vivo as a component of the stable THO complex. Thus, through the combinatorial use of an adaptor (e.g., Aly) and co-adapter (e.g., Thoc5), Tap-p15 could function as an export receptor for different classes of mRNAs.