The orchestration of ciliary opus: Interplay of signalling molecules, GTPases, and trafficking machinery

Primary cilia are sensory organelles that host various signalling receptors and proteins to coordinate signalling pathways essential for tissue homeostasis. This review explores the molecular mechanisms by which intraflagellar transport (IFT) machinery, the BBSome coat complex, small GTPases, and various secondary messenger signalling molecules cooperate to establish and maintain ciliary composition. We discuss how IFT trains, guided by kinesin-2 and dynein-2 motors, traffic receptors and signalling components into and out of the cilium, and how the lipid composition within the cilium plays a regulatory function. We also described how secondary messengers such as cAMP and Ca²⁺ coordinate ciliary signalling outputs, including hedgehog and insulin secretion. Finally, we have also discussed how the BBSome selects cargo for export and the role of small GTPases in its trafficking, together ensuring the compositional integrity and signalling fidelity of this organelle. A mechanistic understanding of these integrated trafficking and signalling systems provides a framework for elucidating the pathogenesis of ciliopathies and identifying potential therapeutic targets.