GPR39 and major depressive disorder: Zinc deficiency gives rise to various neuropsychiatric disorders, including epilepsy, seizures, and depression.479,480 Extracellular zinc can activate zinc-sensing receptor GPR39.481,482 Zinc stimulates GPR39-mediated signal transduction and induces calcium mobilization in HEK293 cells.483 Zinc-activated GPR39 increases expression of K+/Cl− cotransporter 2 (KCC2), the Cl- outward transporter in neurons.484 Further, GPR39 increases Na+/H+ exchanger activity in hippocampal neurons in a pH-dependent process.485