Microtubule inner proteins - bridging structure and function in ciliary biology

Motile cilia are highly specialized organelles that generate rhythmic beating to drive fluid flow and cell movement. This activity depends on the unique molecular machinery of the axoneme, which is composed of hundreds of proteins that operate in a highly coordinated manner. Recent advances in cryo-electron microscopy have uncovered a dense and diverse network of microtubule inner proteins (MIPs) that reside within the lumen of doublet microtubules and the central apparatus. These proteins are arranged in a remarkably ordered architecture and contribute to the mechanical stability, periodic organization and functional regulation of the ciliary axoneme. In this Review, we summarize current structural and functional insights into conserved and lineage-specific MIPs, their roles in shaping ciliary architecture, and the consequences of their disruption on ciliary motility and the resulting ciliopathies. We also highlight emerging approaches that are beginning to reveal the specific contributions of MIPs to axonemal integrity, spatial organization and mechanical stability. Together, these advances are reshaping our understanding of how MIPs regulate ciliary structure and function.