Abstract

The Hippo signaling pathway has emerged as a major player in many aspects of liver biology, such as liver development, cell fate determination, homeostatic function, and regeneration from injury. The regulation of Hippo signaling is complex, with activation of the pathway coming from diverse upstream inputs including signals from cellular adhesion, mechanotransduction, and crosstalk with other signaling pathways. Pathological activation of the downstream transcriptional co-activators yes-associated protein 1 (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), which are negatively regulated by Hippo signaling, has been implicated in multiple aspects of chronic liver disease, such as the development of liver fibrosis and tumorigenesis. As such, development of pharmacological inhibitors of YAP/TAZ signaling has been an area of great interest. In this review, we summarize the diverse roles of Hippo signaling in liver biology and highlight areas where outstanding questions remain to be investigated. Greater understanding of the mechanisms of Hippo signaling in liver function should help to facilitate the development of novel therapies for the treatment of liver disease.