ATP2B3 encodes a plasma membrane calcium ATPase (PMCA3) that functions as an ATP-driven calcium ion pump. The primary role of ATP2B3 is maintaining basal intracellular Ca2+ levels at presynaptic terminals by actively transporting cytosolic calcium ions across the plasma membrane to the extracellular compartment, using ATP hydrolysis as the energy source 1234. The gene is located on chromosome X 5 and shows tissue-specific expression, particularly in the nervous system. Clinically, ATP2B3 mutations have emerged as significant contributors to primary aldosteronism, the most common cause of secondary hypertension. Somatic ATP2B3 mutations are identified in approximately 10-15% of aldosterone-producing adenomas 6789101112. These mutations disrupt intracellular calcium signaling, leading to cell membrane depolarization and subsequent excessive aldosterone production 679. The identification of ATP2B3 as a disease gene has important implications for understanding the genetic basis of hypertension and potentially developing targeted molecular therapies. Additionally, ATP2B3 is a candidate gene for neurological diseases assigned to the distal Xq region 5.