The complex of NPAS4 and ARNT2 directly stimulates transcription of the BDNF gene, based on in vitro studies (Pruunsild et al. 2011). In mouse brain (Lin et al. 2008; Ramamoorthi et al. 2011) and in primary rat neurons (Brigidi et al. 2019), Npas4 was also shown to positively regulate Bdnf gene expression. The NPAS4:ARNT2 complex is shown as a set member, while NPAS4:ARNT and NPAS4:ARNTL are shown as set candidates in the context of transcriptional activation of the BDNF gene.

Based on studies in mouse (Funahashi et al. 2019) and rat (Ooe et al. 2009) model systems, neuronal cell stimulation leads to MAPK1 (and probably MAPK3) mediated phosphorylation of NPAS4 on evolutionarily conserved amino acid residues, which increases transcriptional activity of NPAS4 on target gene promoters such as BDNF, possibly by enabling association of NPAS4 with histone acetyltransferase CREBBP (CBP).