Primary cilium disassembly - from mechanisms to roles in physiology and disease

Primary cilia are micron-scale cellular compartments with key roles in cell signaling and disease. Cilium assembly has been delineated as a multi-step process that is disrupted in ciliopathies, yet many features of cilia disassembly remain incompletely understood. Here, we review recent insights into cilia disassembly. In addition to discussing the longstanding link between cilia disassembly and the cell cycle, we consider new findings that broaden our understanding of the molecular mechanisms and physiological contexts that govern cilia disassembly. We also synthesize recent evidence that mutual antagonism between assembly and disassembly pathways governs ciliation state. Together, these studies reveal that both excessive and impaired disassembly can perturb ciliary signaling and function, with consequences for development, tissue homeostasis and tumorigenesis. Motivated by these advances, we propose a new ciliopathy subclassification - disassembly-related ciliopathies - to encompass diseases in which aberrant cilia disassembly contributes to pathogenesis. Continued exploration of the mechanisms controlling cilia disassembly will provide both fundamental biological insights and open new avenues for targeted treatment of diseases caused by ciliary dysfunction.