Skin-Specific Regulation of SREBP Processing and Lipid Biosynthesis by Glycerol Kinase 5

The study identified that the toku phenotype, which causes delayed hair growth and progressive hair loss, is due to a null allele of the Gk5 gene that encodes glycerol kinase 5 (GK5). GK5, which is predominantly expressed in sebaceous glands, interacts with sterol regulatory element-binding proteins (SREBPs) to inhibit their processing and activation. In mice lacking functional GK5 (Gk5toku/toku), there was an accumulation of transcriptionally active SREBPs in the skin, but not in the liver, leading to increased lipid synthesis and hair growth abnormalities. These defects were also observed in mice with kinase-inactive GK5. Treatment with simvastatin, an HMG-CoA reductase inhibitor, partially improved the hair growth defects in the toku mice. This suggests that GK5 is a key regulator of skin-specific lipid biosynthesis and has a role in hair growth, independent of cholesterol regulation in other parts of the body.