Plasma membrane calcium-transporting ATPase 4

Plasma membrane calcium-transporting ATPase 4 (PMCA4), encoded by ATP2B4, is a calcium/calmodulin-regulated and magnesium-dependent ATPase that catalyzes the active transport of calcium out of cells (UniProt: P23634). This 1241-amino acid protein maintains cellular calcium homeostasis by coupling ATP hydrolysis to calcium efflux, a process essential for regulating intracellular calcium levels.

PMCA4 is expressed in multiple tissues and plays roles in calcium signaling and cell motility. The protein has been implicated in sperm physiology through its regulation of calcium homeostasis (UniProt: P23634). No baseline disease associations are annotated in UniProt for this entry.

In Alzheimer's disease, PMCA4 shows a modest upregulation in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). Analysis of four subcellular fractions (P2, P3, S2, S3) via TMT-labeled tandem mass spectrometry revealed a mean log2 fold-change of 0.1878, indicating slightly elevated protein levels in the AD brain. This subtle elevation may reflect compensatory calcium-handling responses or altered cellular compartmentalization in neurodegeneration.