In summary, our 12-O-Tiglylphorbol-13-isobutyrate results indicate that the loss of SHP immunoreactivity is a commonly observed change during hepatocellular carcinoma development, and is even more pronounced in the fibrolamellar one. Rab family proteins are known to function in intracellular membrane trafficking. They participate in many biological processes, including endocytosis and exocytosis, cytokinesis, melanosome formation, autophagosome formation, lysosome Tiotropium Bromide hydrate biogenesis, and signaling transduction. The identification of Rabs in lipid droplet proteomic studies suggests a potential role for Rabs in regulating the dynamics of lipid droplets and/or lipid storage. Indeed, the recruitment of Rab18 to lipid droplets is regulated by the metabolic state of lipid droplets, implying that Rab18 may mobilize lipids stored in lipid droplets. Although a start has been made in exploring the roles of Rab18 in lipid droplets, the functions of the majority of Rab proteins identified in proteomic studies in lipid storage are still unclear. In addition, it is possible that other Rabs which have not yet been identified in proteomic studies may also have roles in lipid storage and metabolism. For example, a whole genome RNAi screen of S2 cells showed that about 1.5% of all the genes tested function in lipid droplet formation and utilization. Another RNAi screen in adult flies identified about 500 obesity genes. The Hedgehog signaling pathway was shown to have a fat body-specific role in Drosophila and to function as a switch between brown and white adipose tissues in mammals, suggesting that fat storage mechanisms are conserved between Drosophila and mammals. In this study, we have systemically investigated the potential roles of Rab proteins in the regulation of lipid storage in Drosophila. As a small GTPase, Rab protein can switch between its GDPbinding inactive form and GTP-binding active form. Guanine nucleotide exchange factor switches GTPase from its inactive to its active form, while GTPase activating protein inactivates GTPase. With the help of structural and functional analysis, specific amino acid changes can be made that keep Rab GTPase in its GDP-binding form or GTP-binding form. Expression of the DN or CA form can therefore mimic loss-of-function or gain-offunction effects.