The aim of this study was the phenotypic and functional analyses of neurochondrin (Ncdn ) gene–trap mouse mutant. This mouse line expresses a truncated form of Ncdn due to integration of the gene-trap vector pT1bettageo in Exon 7. The homozygous females are subfertile due to ovulation failure. The analyses of factors involved in the regulation of the female fertility revealed dramatically elevated level of prolactin (PRL) expression in the pituitary of female mutants. The pituitaries itself were enlarged and contained an increased number of proliferating lactotrophs, as a consequence of decreased Erk1/2 activity in the anterior lobe. In fact, PRL expression and lactotroph proliferation are under negative control of neurotransmitter dopamine (DA) via activation of the dopamine receptor 2 (D2R). Interestingly, D2R contains the Ncdn-binding-domain and shows similar expression pattern with Ncdn in the pituitary. Moreover, the pituitary phenotype of Ncdn trapped mice strongly resembles to the one of D2R knock outs.These findings suggested a possible involvement of Ncdn in D2R signalling in the pituitary.