The CPLANE complex is essential for ciliogenesis, and mutations to all but one subunit have been associated with ciliopathies. Here they identify three familial mutations in the final subunit, RSG1, t...

ALT: a woman in a long black dress is walking down a foggy street .

Using a broad panel of ciliopathy iPSC-retinal pigment epithelium (RPE) new approach models, Reichert et al. identified shared cellular endophenotypes across patients, including mesenchymal drift and loss of polarization. Mechanistic studies implicated mitochondrial dysfunction and aberrant TGF-β signaling in RPE pathology. Drug screening identified pioglitazone and galunisertib as candidate therapeutics.

Motile cilia are ancient, evolutionarily conserved organelles whose dysfunction underlies motile ciliopathies, a broad class of human diseases. Motile…

The temporospatial distribution of proteins within cilia is regulated by intraflagellar transport (IFT), wherein molecular trains shuttle between the cell body and cilium. Defects in this process impair various signal-transduction pathways and cause ciliopathies. Although K63-linked ubiquitination appears to trigger protein export from cilia, the mechanisms coupling polyubiquitinated proteins to IFT remain unclear. Using a multidisciplinary approach, we demonstrate that a complex of CFAP36, a conserved ciliary protein of previously unknown function, and ARL3, a GTPase involved in ciliary import, binds polyubiquitinated proteins and links them to retrograde IFT trains. CFAP36 uses a coincidence detection mechanism to simultaneously bind two IFT subunits accessible only in retrograde trains. Depleting CFAP36 accumulates K63-linked ubiquitin in cilia and disrupts Hedgehog signaling, a pathway reliant on the retrieval of ubiquitinated receptors. These findings advance our understanding of ubiquitin-mediated protein transport and ciliary homeostasis, and demonstrate how structural changes in IFT trains achieve cargo selectivity. ### Competing Interest Statement The authors have declared no competing interest. Sara Elizabeth O'Brien Trust Postdoctoral Fellowship awarded through the Charles A. King Trust Postdoctoral Research Fellowship Program, , 8460873-01 Richard and Susan Smith Family Foundation, https://ror.org/05j95n956, National Institute of General Medical Sciences (NIGMS), , R01GM141109, R01GM143183

Primary cilia orchestrate several signaling pathways, and their disruption results in pleiotropic disorders called ciliopathies. Bardet Beidl syndrome (BBS), one such ciliopathy, provides insights int...

Increasing evidence suggests that anesthesia may induce developmental neurotoxicity, yet the influen

European Journal of Human Genetics - Complete loss of IFT27 function leads to a phenotypic spectrum of fetal lethal ciliopathy associated with altered ciliogenesis