The members of the PAT (SLC36) family of transporters characterized to date have been shown to be proton-coupled amino acid transporters, with alanine, glycine and proline as the major physiological substrates (Boll et al. 2004). Recently we reported that the Drosophila melanogaster protein CG1139, with ~30% identity to the mammalian PATs, is also a proton-coupled alanine, glycine and proline transporter (Meredith et al. 2005). The gene path from Drosophila melanogaster encodes a protein (PATH) with a predicted open reading frame of 471 amino acids which also has ~30% amino acid identity to mammalian PATs, and a 38% identity to CG1139. PATH (short for Pathetic), was so-named because disruption of the path gene in Drosophila results in a small fly phenotype, implicating this transporter in a nutrient sensing role in the control of growth (Goberdhan et al. 2005). Here we provide evidence that although path does encode an amino acid transporter, it has different functional characteristics to the mammalian PAT and CG1139 transporters. The path clone (CG3424) was obtained from the Drosophila Genomics Resource Centre and expressed in Xenopus laevis oocytes. Uptake of [³H]-Ala (75nM) was measured using the method described in Goberdhan et al. (2005). The uptake of alanine was fastest when the external pHout was 7.4, with uptake abolished by extracellular acidification (Fig. 1A, 79.1 ± 17.9 versus 11.8 ± 11.9 fmoles/oocyte/h, mean ± S.E.M., pHout 7.4 versus 5.5, respectively, n=5 oocytes, p<0.001 Student's t test). The affinity for alanine was very high (apparent Km 2.7 ± 1.0μM at pHout 7.4 (Fig. 1B), and uptake was inhibited by glycine (by 76 ± 5%, p<0.001) but not proline (13 ± 8%, p=0.31) (both 50μM, data not shown). In conclusion, PATH is an amino acid transporter with much higher affinity than the mammalian PATs (mouse PAT1 and PAT2 Km for alanine of 7.5 and 0.26 mM, respectively, when expressed in oocytes; Boll et al. 2002) and the recently characterized Drosophila protein CG1139 (1.2mM, Meredith et al. 2005; Goberdhan et al. 2005). In addition, transport through PATH is not stimulated by extracellular protons, and indeed at pHout 5.5 there was virtually no uptake. These very high affinity/very low capacity transport characteristics, taken together with the finding that disrupting the path gene results in a small fly phenotype, suggest a role for PATH as an amino acid sensor involved in the control of growth.