In this study, we examined the non‐visual behavioral and gene expression consequences of Gpr143‐gene knockout and found that the gene‐deficient (Gpr143−/y) mice exhibited a complex phenotype unlikely related to visual deficits, including behavior associated with schizophrenia (e.g., impaired prepulse inhibition (PPI)) yet also behavior associated with mood or affective disorders (e.g., depression; excessive reward responsiveness; heightened aggression and social dominance). The gene discussed is GPR143; the disease is major depressive disorder.