Based on studies in mouse olfactory bulb neurons, NPAS4 directly represses transcription of MDM2. NPAS4-mediated repression of MDM2 is needed to increase dendritic spine density through prevention of MDM2-mediated ubiquitination and degradation of microtubule-associated protein DCX (Yoshihara et al. 2014), involved in neuronal dispersion and lamination. In mouse hippocampus, NPAS4 was also shown to negatively regulate MDM2 expression, which interferes with MDM2-mediated ubiquitination and degradation of the postsynaptic density protein DLG4 (PSD-95) (Lv et al. 2021). In primary cultures or rat neurons, where binding of Npas4, Arnt and Arnt2 to the Mdm2 gene locus was demonstrated via high-throughput ChIP-seq, no significant change in Mdm2 expression levels by RNA-seq was detected upon Npas4 activation (Brigidi et al. 2019).