The CIDEC protein is located in lipid droplets (LDs) and the endoplasmic 
reticulum (ER) and is induced in fat deposition. However, the binding domain, 
the functional domain and the underlying mechanism of CIDEC in stimulating lipid 
accumulation remain unclear. Here, we investigated the subcellular localization 
and function of pig CIDEC and confirmed CIDEC promotes unilocular development of 
LDs, reduces the specific surface area (SSA) of LDs and stimulates lipid 
accumulation in HepG2 cells. By analyzing a series of CIDEC mutants, we showed 
the N-domain (1-173 amino acid) is involved in LD localization and the C-domain 
(174-238 amino acid) is necessary for LD fusion. Further analysis indicated that 
the 106-173 amino acid region includes an ER-binding domain. Moreover, CIDEC 
stayed in the ER under lipid-deficient conditions and translocated to LDs under 
fatty acid stimulation suggesting that localization of CIDEC in the ER is before 
the LD. Our data indicated additional fatty acids stimulated hepatic CIDEC 
expression and an increasing level of CIDEC induced hepatic LD fusion and lipid 
accumulation. Our work suggests that CIDEC protects LDs by decreasing the SSA of 
LDs and is involved in the regulation of hepatic lipid deposition.