Structure Makes a Difference: IFT Complex in Ciliary Function and Ciliopathy.

Cilia, evolutionarily conserved organelles on eukaryotic cell surfaces, depend on the intraflagellar transport (IFT) system for their assembly, maintenance, and signaling. The IFT system orchestrates bidirectional trafficking of structural components and signaling molecules through coordinated actions of protein complexes and molecular motors. IFT complexes assemble into anterograde trains at the ciliary base and undergo structural remodeling at the ciliary tip to form retrograde trains, with bidirectional motility regulated by modifications on the trains per se and the microtubule tracks. The BBSome rides with the IFT train and serves as a pivotal adaptor linking membrane cargos to the IFT train primarily for cargo exit from the cilia. Mutations in cilium-related genes from human ciliopathies contribute to the understanding of the IFT machinery. This review comprehensively delineates the molecular architecture, transport mechanisms, and regulatory networks of IFT complexes, bridging their functional dysregulation to disease phenotypes and advancing mechanistic insights.