Primary cilia: sensors of biliary homeostasis and disease

The primary cilium (plural 'cilia') is a highly specialized organelle found on nearly every vertebrate cell. It functions as a sensor, cell cycle regulator and coordinator of multiple signalling transduction pathways. In cholangiocytes, primary cilia extend from the cell surface into the bile duct lumen, acting as chemosensors, mechanosensors and osmosensors in response to changes in bile composition and flow. This primary-cilium-mediated sensing regulates the biliary microenvironment and is crucial to maintaining homeostasis and promoting biliary regeneration. Moreover, alterations in the structure or function of cholangiocyte primary cilia lead to a group of disorders known as biliary ciliopathies, which manifest with a broad range of clinical features including cystic lesions, fibrosis and biliary strictures. This Review aims to provide an overview of the structure and function of cholangiocyte primary cilia and to summarize the known biliary ciliopathies. As most of these diseases currently lack effective treatments targeting their underlying mechanisms, an understanding of this organelle can help to pave the way for novel cilium-targeted therapies.