Furthermore, a relevant aspect is that although SD begins in neurons and other cell types of the NVU are only secondarily involved,31, , –34 the dysfunction causative for the initiation of SD in neurons may well be of astrocytic origin.35 This has been particularly well evidenced, for example, for familial hemiplegic migraine type 2 (FHM2), a rare Mendelian model disease of SD due to loss-of-function mutations in ATP1A2, the gene encoding the α2 isoform of Na+/K+-ATPase (NaKA).36, , , , –41. This evidence concerns the gene ATP1A2 and familial or sporadic hemiplegic migraine.