In conclusion, the alterations in reelin expression in both the CNS and periphery in depression (and in animal models of depression), the analysis of the functional roles of reelin (and dysfunctions in depression), and the observation of how reelin can rescue behavioral phenotypes in different paradigms, strongly suggest that systematically tackling the reelin system may be a good strategy for developing novel antidepressants. Here, RELN is linked to major depressive disorder.