Adipose tissue is central to the regulation of lipid metabolism. 
Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2), one of the most 
severe lipodystrophy diseases, is caused by mutation of the Seipin gene. Seipin 
plays an important role in adipocyte differentiation and lipid homeostasis, but 
its exact molecular functions are still unknown. Here, we show that Seipin 
physically interacts with the sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) 
in both Drosophila and man. SERCA, an endoplasmic reticulum (ER) calcium pump, 
is solely responsible for transporting cytosolic calcium into the ER lumen. Like 
dSeipin, dSERCA cell-autonomously promotes lipid storage in Drosophila fat 
cells. dSeipin affects dSERCA activity and modulates intracellular calcium 
homeostasis. Adipose tissue-specific knockdown of the ER-to-cytosol calcium 
release channel ryanodine receptor (RyR) partially restores fat storage in 
dSeipin mutants. Our results reveal that Seipin promotes adipose tissue fat 
storage by regulating intracellular calcium homeostasis.