The high correlation of the human PRG-1R345T/WT endophenotype to the corresponding Prg-1 related phenotype in mice suggests that ATX-inhibition, which restored the E/I balance in Prg-1 deficient mice to normal values, has high translational potential for a therapeutic intervention for cortical hyperexcitability-related mental disorders. The gene discussed is ENPP2; the disease is mental disorder.