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Significance Cilia are composed of hundreds of proteins whose identities and functions are far from being completely understood. In this study, we determined that calmodulin-regulated spectrin-associated protein 3 (CAMSAP3) plays an important role for the function of motile cilia in multiciliated cells (MCCs). Global knockdown of CAMSAP3 protein expression in mice resulted in defects in ciliary structures, polarity, and synchronized beating in MCCs. These animals also displayed signs and symptoms reminiscent of primary ciliary dyskinesia (PCD), including a mild form of hydrocephalus, subfertility, and impaired mucociliary clearance that leads to hyposmia, anosmia, rhinosinusitis, and otitis media. Functional characterization of CAMSAP3 enriches our understanding of the molecular mechanisms underlying the generation and function of motile cilia in MCCs.

CAMSAP3 facilitates basal body polarity and the formation of the central pair of microtubules in motile cilia