– ATP1B4 is a member of the X(+)/potassium ATPases subunit beta family. It is highly expressed in skeletal muscle and at a lower level in heart. ATP1B4 gene can be found in all vertebrate genomes sequenced to date. However, this gene has undergone a change in function in placental mammals compared to other species. Specifically, in fish, avian, and amphibian species, this gene encodes plasma membrane-bound beta-subunits of Na, K-ATPase. In placental mammals, the encoded protein interacts with the nuclear transcriptional coregulator SKIP and may be involved in the regulation of TGF-beta signaling. ATP1B4 may act as a transcriptional coregulator during muscle development through its interaction with SNW1. Na+, K+-ATPase is an important regulator of intracellular electrolyte levels in most mammalian cells. It is a Mg2+-dependent transport pump responsible for maintaining the low intracellular Na+:K+ ratio that is essential for cell homeostasis and physiological function. It catalyzes the active uptake of K+ and extrusion of Na+ at the expense of hydrolyzing ATP with a stoichiometry of 3 Na+ for 2 K+. ATP1B4 has lost its ancestral function as a Na,K-ATPase beta-subunit.