RESEARCH HIGHLIGHTS Nature Reviews Nephrology | Published online 23 May 2016; doi:10.1038/nrneph.2016.74 CILIOPATHIES CPLANE regulates intraflagellar transport Recent research has identified a new of oro–facial–digital syndrome (OFD). protein complex with an important role Consistent with this finding, the researchers mutations in ciliogenesis and in human ciliopathies, identified disease-associated mutations in CPLANE including disorders that affect the kidney. in WDPCP and/or INTU in the exomes of John Wallingford and coworkers show that patients with ciliopathies (nephronophthisis, components ciliogenesis and planar cell polarity effector OFD and short-rib polydactyly syndrome) are associated (CPLANE), a complex formed by Inturned or ciliopathy features (cerebellar vermis with (Intu), Fuzzy and Wdpcp, recruits a specific hypoplasia, ataxia, and retinal dystrophy). ciliopathies in subset of intraflagellar transport (IFT) “What is remarkable is that none of proteins to the cilium and that mutations in the CPLANE proteins are particularly patients and in CPLANE components are associated with well-studied, which highlights the impor- mouse models ciliopathies in patients and in mouse models. tance of the ‘ignorome’ — the huge body The researchers report that the CPLANE of proteins encoded by the human genome proteins form a physical and functional that remain poorly studied or even entirely unit with the ciliopathy-associated protein unstudied,” remarks Wallingford. Moving Jbts17 and the small GTPase Rsg1. Jbts17 forward, the researchers’ efforts will focus localizes CPLANE to the base of the cilium on the biochemical characterization of where the complex specifically recruits the CPLANE and a broad and extensive search peripheral proteins of the multiprotein IFT for CPLANE mutations in patients with complex, IFT-A. “These data provide the first ciliopathies. demonstration that cytoplasmic factors are Andrea Aguilar specifically required for the recruitment and ORIGINAL ARTICLE Toriyama, M. et al. The ciliopathy- assembly of IFT particles,” notes Wallingford. associated CPLANE proteins direct basal body recruitment of In mice, mutations in CPLANE proteins intraflagellar transport machinery. Nat. Genet. http://dx.doi. led to developmental defects reminiscent org/10.1038/ng.3558 (2016) NATURE REVIEWS | NEPHROLOGY www.nature.com/nrneph ©2016 Mac millan Publishers Li mited. All ri ghts reserved. .