For monogenic migraine, mapping of loci in family pedigrees, coupled with genomic sequencing to find variants, led to the discovery of the main FHM genes, CACNA1A, ATP1A2 and SCN1A. Knowledge of their roles as ion channels and in ion transport, along with functional experiments in cellular and animal models, has contributed to uncovering how their dysfunction may lead to cortical hyperexcitability and migraine. The gene discussed is ATP1A2; the disease is migraine disorder.