Lipin-1γ isoform is a novel lipid droplet-associated protein highly expressed in the brain.

Lipin-1 proteins are phosphatidic acid phosphatases (PAPs) catalyzing the conversion from phosphatidic acid (PA) to diacylglycerol (DG). Two alternative splicing isoforms, lipin-1α and -1β, are localized at different subcellular compartments. A third splicing isoform, lipin-1γ was recently cloned and its subcellular localization is unknown. Here, we demonstrate that lipin-1γ is localized to lipid droplets (LDs), an association mediated by a hydrophobic, lipin-1γ-specific domain. Additional expression of lipin-1γ altered LD morphology without affecting the triacylglycerol (TG) level. In human tissues, lipin-1γ is the main lipin-1 isoform expressed in normal human brain, suggesting a specialized role in regulating brain lipid metabolism.