Familial hemiplegic migraine (FHM) is a rare, autosomal dominant subtype of migraine, associated in half of the families with mutations in the CACNA1A gene located on chromosome 19p13, which encodes the Cav2.1-subunit of brain-specific P/Q-type calcium channels. Recently, mutations in a second gene, ATP1A2 on chromosome 1q23, which encodes a sodium-potassium exchange pump subunit, have been identified. The first functional studies indicate that A TP1A2 FHM mutations result in a loss of function of the pump, leading to an increase in extracellular potassium. This is known to evoke cortical spreading depression, the underlying mechanism of migraine aura.