Arl3 is highly conserved in ciliated organisms, and has been shown to localise throughout the cell and is enriched in the primary cilium. In the cilium, Arl3 acts as a transporter of cargo from the pre-ciliary compartment into the ciliary axoneme. Arl3 has been shown to specifically transport carrier proteins of prenylated, farnesylated and geranylgeranylated cargo (PDE6δ) and myristolyated cargo (UNC119a/b).
ADP-riboslyation factor-like 3 (Arl3) is part of the RAS superfamily of low molecular weight GTP-binding proteins which consists of 4 subfamilies; Ras, Rab, Rho and Arf. Ras-related superfamily proteins act as molecular switches cycling between an inactive GDP-bound and an active GTP-bound form. The rate of cycling between the two states is determined by the interactions with the associated guanosine nucleotide exchange factor (GEF), Arl13b, and the GTPase activating protein (GAP), Retinitis pigmentosa 2 (RP2). Arl proteins have a highly conserved glycine residue at position 2; which is where N-myristolytion occurs. However, they lack intrinsic GTP hydrolysis activity which suggests that they interact with other proteins or molecules to hydrolyse GTP to GDP.
2 mutations in 2 families have been identified in ARL3, both are missense mutations affecting the same amino acid residue in the protein (Arg149). This residue is highly conserved throughout evolution and mutations here disrupt the interaction between Arl3 and Arl13b, affecting the function of Arl3 in the trafficking of ciliary proteins.