Isoform D of Plasma membrane calcium-transporting ATPase 1

ATP2B1 (isoform D) encodes the plasma membrane calcium-transporting ATPase 1, a key regulator of intracellular calcium homeostasis. This protein uses ATP hydrolysis to extrude calcium from the cell, maintaining the steep calcium gradient essential for neuronal signaling and cellular function (UniProt: P20020-1).

The protein is broadly expressed across tissues with particular importance in the nervous system, where calcium dysregulation is implicated in neurodegeneration. Calcium pump dysfunction has been associated with impaired synaptic transmission and cellular stress responses. ATP2B1 variants have been linked to hypertension in genome-wide association studies, reflecting its role in vascular and neural calcium control.

In Alzheimer's disease, ATP2B1 isoform D is significantly upregulated in post-mortem brain tissue from AD patients compared to age-matched controls (mean log2FC = 0.53; Chaparral AD proteomics). This increase may represent a compensatory response to calcium dysregulation characteristic of AD pathology. Calcium homeostasis dysfunction and amyloid-beta toxicity are known to exacerbate neurodegeneration, making calcium pump upregulation potentially relevant to AD-associated neuronal stress and decline.