Nab2 is constructed from an N-terminal PWI-fold domain, followed by QQQP and RGG motifs and then seven CCCH Zn fingers. The nuclear pore-associated proteins Gfd1 and Mlp1 bind to opposite sides of the Nab2 N-terminal domain and function in the nuclear export of mRNA, whereas the Zn fingers bind to A-rich regions of mature transcripts and function to regulate poly(A) tail length as well as mRNA compaction before nuclear export. NGF1-A-binding protein 2 (Nab2) is a conserved transcriptional cofactor that directly binds to Egr-1 and positively or negatively modulates Egr-1 target gene transcription. Nab2 is a novel endogenous negative regulator of Egr-1-dependent TGF-beta signaling responsible for setting the intensity of fibrotic responses. Defective Nab2 expression or function in dermal fibroblasts might play a role in persistent fibrotic responses in scleroderma. Mutations in the gene encoding the human Nab2 orthologue ZC3H14 and cause intellectual disability.