Cilia and flagella are fascinating organelles that can be seen as thin membrane-bound projections extending from the body of various cell types. Most well-known are the flagella of sperm cells and the motile cilia that are present in epithelial cells of the lungs and fallopian tubes, as well as ependymal cells of the brain ventricles. These types of cilia mediate movement. However, there is a third type of cilia, which are non-motile and present in most human cell types, referred to as primary cilia.

Primary cilia are usually present in a single copy per cell. Rather than mediating movement, primary cilia seem to act as sensory organelles that react to a wide range of stimuli from the environment. For example, primary cilia of renal epithelial cells mediate the sensation of liquid flow at the cell surface. Other primary cilia can detect light, gravity, chemicals, and/or osmolarity. With this plethora of receptor functions, primary cilia are emerging as a hub for cell signaling, with important roles in various organs and in fundamental processes such as development and memory. Indeed, defects in genes encoding proteins related to the structure and function of primary cilia cause a wide range of human diseases, collectively known as ciliopathies. These range from polycystic kidney disease (PKD) to the highly pleiotropic Bardet-Biedl syndrome (BBS). The latter is characterized by a wide array of symptoms involving various tissues and cell types, including vision loss, diabetes, obesity, kidney dysfunction, learning disabilities and developmental defects.

While the importance of primary cilia in the human body is now being recognized, rather little is known about the molecular mechanisms behind primary cilia function. For example, there are only a few signal transduction pathways that have been clearly attributed to primary cilia. One key to closing this knowledge gap is likely to be a detailed study of the dynamic protein composition of individual cilia. Therefore, the team behind the subcellular section of the Human Protein Atlas are currently leveraging the extensive antibody library of the Human Protein Atlas to systematically map proteins that localize to primary cilia of various cell types. The use of imaging-based spatial proteomics allows the study of detailed protein distribution at a single-cell level and in relation to cellular states.