Primary ciliary dyskinesia (PCD) is a genetically heterogeneous autosomal 
recessive disorder characterized by recurrent infections of the respiratory 
tract associated with the abnormal function of motile cilia. Approximately half 
of individuals with PCD also have alterations in the left-right organization of 
their internal organ positioning, including situs inversus and situs ambiguous 
(Kartagener's syndrome). Here, we identify an uncharacterized coiled-coil domain 
containing a protein, CCDC40, essential for correct left-right patterning in 
mouse, zebrafish and human. In mouse and zebrafish, Ccdc40 is expressed in 
tissues that contain motile cilia, and mutations in Ccdc40 result in cilia with 
reduced ranges of motility. We further show that CCDC40 mutations in humans 
result in a variant of PCD characterized by misplacement of the central pair of 
microtubules and defective assembly of inner dynein arms and dynein regulatory 
complexes. CCDC40 localizes to motile cilia and the apical cytoplasm and is 
required for axonemal recruitment of CCDC39, disruption of which underlies a 
similar variant of PCD.