Plasma membrane calcium-transporting ATPase 4 (ATP2B4)

Plasma membrane calcium-transporting ATPase 4 (ATP2B4, also known as PMCA4) is a calcium/calmodulin-regulated and magnesium-dependent P-type ATPase that catalyzes the ATP-driven export of Ca²⁺ from the cytoplasm across the plasma membrane, playing a critical role in intracellular calcium homeostasis[1][3][5]. The ATP2B4 gene is highly expressed in the heart, brain, adrenal glands, and other tissues, with alternative splicing generating isoforms adapted to specific cell types[1][2][3]. PMCA4 activity is crucial for terminating calcium-mediated signaling and maintaining low basal cytosolic Ca²⁺, which is important for cellular survival, signal transduction, and specialized functions such as neurotransmission, muscle contraction, and sperm motility[1][3][5]. Dysregulation or rare variants in ATP2B4 are associated with disorders including spastic paraplegia, hypertension, and may contribute to aldosterone dysregulation in primary aldosteronism[2][3]. PMCA4 is experimentally validated as interacting with scaffold proteins (e.g., CASK), and, while not directly targeted by approved drugs, it constitutes a key enzyme/transporter in calcium signaling and homeostasis with relevance as a potential therapeutic target[1][4][5].

Other names

PMCA4Plasma membrane calcium ATPase isoform 4ATP2B2MXRA1Matrix-remodeling-associated protein 1ATPase, Ca++ transporting, plasma membrane 4Plasma membrane calcium pump isoform 4PMCA4bPMCA4x

Inhibition or modulation leads to increased intracellular calcium concentration, potentially affecting cell signaling and contractility. Enhancement (if achievable pharmacologically) would reduce cytosolic calcium.