SPCA1 pumps and Hailey–Hailey disease

Both the endoplasmic reticulum and the Golgi apparatus are agonist-sensitive intracellular Ca 2+ stores. The Golgi apparatus has Ca 2+-release channels and a Ca 2+-uptake mechanism consisting of sarco(endo)plasmic-reticulum Ca 2+-ATPases (SERCA) and secretory-pathway Ca 2+-ATPases (SPCA). SPCA1 has been shown to transport both Ca 2+ and Mn 2+ in the Golgi lumen and therefore plays an important role in the cytosolic and intra-Golgi Ca 2+ and Mn 2+ homeostasis. Human genetic studies have provided new information on the physiological role of SPCA1. Loss of one functional copy of the SPCA1 ( ATP2C1) gene causes Hailey–Hailey disease, a skin disorder arising in the adult age with recurrent vesicles and erosions in the flexural areas. Here, we review recent experimental evidence showing that the Golgi apparatus plays a much more important role in intracellular ion homeostasis than previously anticipated.