ARL3 is a small GTP-binding protein that regulates the spatial distribution of lipid-modified proteins in cilia and other cellular compartments 1. It cycles between inactive GDP-bound and active GTP-bound states, with this cycling regulated by guanine nucleotide exchange factors (GEFs) like ARL13B and GTPase-activating proteins (GAPs) like RP2 2. ARL3 functions as a cargo displacement factor, releasing lipidated proteins from solubilizing carriers (PDE6D and UNC119) to enable their selective delivery to ciliary membranes 3. This process is critical for targeting myristoylated and prenylated proteins essential for ciliogenesis and ciliary signaling 1. Additionally, ARL3 participates in ubiquitin-mediated protein retrieval from cilia by binding K63-linked polyubiquitinated proteins and coupling them to retrograde intraflagellar transport 4. ARL3 also regulates senescence initiation through a ciliary ARL13B-ARL3 cascade that controls transition fiber protein interactions 5. Mutations in ARL3 cause dominant non-syndromic retinitis pigmentosa and are implicated in ciliopathies including Joubert syndrome 61. Loss of ARL3 is embryonically lethal, while dysregulation impairs photoreceptor ciliogenesis and cargo trafficking, leading to photoreceptor degeneration 2.