Lipid droplets are found in all cell types. Normally present at low levels in 
the brain, they accumulate in tumours and are associated with neurodegenerative 
diseases. However, little is known about the mechanisms controlling their 
homeostasis in the brain. We found that GRAF1a, the longest GRAF1 isoform (GRAF1 
is also known as ARHGAP26), was enriched in the brains of neonates. Endogenous 
GRAF1a was found on lipid droplets in oleic-acid-fed primary glial cells. 
Exclusive localization required a GRAF1a-specific hydrophobic segment and two 
membrane-binding regions, a BAR and a PH domain. Overexpression of GRAF1a 
promoted lipid droplet clustering, inhibited droplet mobility and severely 
perturbed lipolysis following the chase of cells overloaded with fatty acids. 
Under these conditions, GRAF1a concentrated at the interface between lipid 
droplets. Although GRAF1-knockout mice did not show any gross abnormal 
phenotype, the total lipid droplet volume that accumulated in GRAF1(-/-) primary 
glia upon incubation with fatty acids was reduced compared to GRAF1(+/+) cells. 
These results provide additional insights into the mechanisms contributing to 
lipid droplet growth in non-adipocyte cells, and suggest that proteins with 
membrane sculpting BAR domains play a role in droplet homeostasis.