Human Mutations in Arl3, a Small GTPase Involved in Lipidated Cargo Delivery to the Cilia, Cause Retinal Dystrophy

Photoreceptors are highly polarized sensory neurons. Precise localization of signaling molecules within the ciliary outer segment is critical for photoreceptor function and viability. The small GTPase Arl3 plays a particularly important role in photoreceptors as it regulates outer segment enrichment of lipidated proteins essential for the visual response: transducin-α, transducin-γ, PDEα, PDE β, and Grk1. Recently, mutations in Arl3 have been identified in human patients with nonsyndromic autosomal recessive and dominant inherited retinal degenerations as well as syndromic Joubert syndrome including retinal dystrophy.