ARL3 and Joubert syndrome: As RP2 is a GAP for ARL3, it is possible that increasing RP2 to a high level would inhibit the production of ARL3-GTP and mimic the effect of loss of the ARL3 GEF, ARL13b, which causes Joubert syndrome; however, this might not occur in the cellular context because of the spatial separation of the proteins, with RP2 predominantly at the base of the cilium and ARL13b in the axoneme, which leads to a gradient of ARL3-GTP in the cilium.