Plasma membrane calcium-transporting ATPase 2 (ATP2B2)

Plasma membrane calcium-transporting ATPase 2 (ATP2B2) is a P-type ATPase enzyme responsible for exporting Ca2+ ions from the cytoplasm to the extracellular space, thereby maintaining low intracellular calcium concentrations critical for cell function[1][3][5]. ATP2B2 is highly expressed in specialized cells, such as cochlear and vestibular hair cells, cerebellar Purkinje neurons, and lactating mammary epithelia, where it is fundamental for auditory transduction, balance, neurodevelopment, and calcium transport in milk[3][4]. Mutations in ATP2B2 are a recognized cause of hereditary deafness (DFNA82) and are associated with a spectrum of neurodevelopmental disorders, including ataxia, dystonia, intellectual disability, epilepsy, and autism[2][4]. The gene produces multiple alternatively spliced isoforms, enabling tissue- and cell type-specific regulation of calcium export, and loss of function or alteration can result in severe sensory and motor deficits as well as broader cognitive and developmental phenotypes[3][4]. ATP2B2 is not a current direct therapeutic target, but it is relevant to strategies modulating calcium homeostasis and is implicated in diseases, including cancer, where calcium-dependent signaling drives pathological cell proliferation or survival[6]. Key literature: - Plasma membrane calcium-transporting ATPase 2 is an ATP-dependent enzyme and transporter regulating intracellular calcium[1][5]. - Crucial for auditory, cerebellar, and neurodevelopmental function; mutations cause hereditary deafness and neurodevelopmental syndromes[2][3][4]. - No approved drugs directly target ATP2B2; manipulation of related pathways or Ca2+ gradients could influence its physiological roles[5][6]. - Principal safety concern: systemic inhibition would likely impair essential neuronal, muscular, and sensory function[2][4].

Other names

PMCA2plasma membrane calcium ATPase isoform 2plasma membrane Ca2+ pump 2DFNA82PMCA2aPMCA2iATPase, Ca++ transporting, plasma membrane 2plasma membrane Ca(2+)-ATPaseplasma membrane calcium pumpATPase plasma membrane Ca2+ transporting 2

ATP-dependent export of Ca2+ from the cytosol to the extracellular space, critical for calcium homeostasis in excitable tissues such as neurons, hair cells, and muscle. Drugs that target calcium gradients or modulate PMCA2 stability or activity could alter cell excitability and signaling