We report on three families in which CPLANE2/RSG1 variants are associated with Oral-Facial-Digital syndrome. Experiments in Xenopus reveal these missense variants to be “separation of function” alleles for Rsg1. Because one of the disease variants is within the GTP-binding pocket of the Rsg1 GTPase, we then used APMS in mouse cells to identify the GTP-dependent interactome of Rsg1, which led us to discover that Rsg1 binds directly to the lipid-binding BAR domain protein Fam92, itself a ciliopathy gene that encodes component of the ciliary transition zone. Finally, using experiments in human cells, we show that Rsg1 is required not only for ciliogenesis but also for Fam92a recruitment to basal bodies. Finally, we show that recruitment of transition zone components is a general function of the CPLANE complex, not restricted to Rsg1.