The Hippo pathway has emerged as a critical developmental pathway contributing to processes that regulate tissue growth and organ size.Our research group aims to characterize the regulation and physiologic functions of the Mst1 and Mst2 protein kinases, which are the mammalian orthologs of the "hippo" kinase.Recently, we have made several exciting discoveries regarding the physiological functions of these two kinases.At first, we conditionally deleted both of Mstl and Mst2 in the developing mouse liver.Within a few weeks, these mice exhibit a dramatic expansion of undifferentiated cells that resemble bipotential liver progenitors.Remarkably, these mice invariably go on to develop both hepatocellular carcinoma and cholangiocarcinoma within four months.In addition, the combined deletion of Mst1 and Mst2 from the hematopoietic compartment results in a profound immunodeficiency syndrome.The liver phenotype reflects an essential, overlapping function of Mst1 and Mst2 in the negative regulation of liver cell proliferation,whereas the immune cell phenotype reflects predominantly the loss of Mstl/2-mediated regulation of cell cytoskeleton and ROS production.