Intriguingly, the Piccolo C2A domain has been reported to regulate the surface levels of dopamine transporters (DAT; Cen et al., 2008), and when over-expressed in transgenic mice to induce depression-like behaviors (Furukawa-Hibi et al., 2010), implying a role for Piccolo in dopaminergic transmission. This evidence concerns the gene SLC6A3 and depressive disorder.