The SLC6 gene family comprises membrane proteins that transport neurotransmitters, amino acids, or osmolytes. We report the first functional characterization of the human SLC6A15 gene, which codes for a sodium-coupled branched-chain amino-acid transporter I (SBAT1). SBAT1 expression is specific to the brain. When expressed in Xenopus oocytes, SBATI mediated Na+-coupled transport of hydrophobic, zwitterionic a-amino and imino acids. SBAT1 exhibited a strong preference for branched-chain amino acids (BCAA) and methionine (K-0.5 80-160 mu M). SBAT1 excluded aromatic or charged amino acids, P-amino acids, glycine, and GABA. SBAT1-mediated transport of amino or imino acids was extremely temperature-dependent (Q(10) = 9) and was inhibited at acidic pH. PKC activation reduced the plasma-membrane population of SBATI protein. SBAT1-mediated transport of BCAA, particularly leucine, may be an important source of amino nitrogen for neurotransmitter synthesis in glutamatergic and GABAergic neurons. (c) 2005 Elsevier Inc. All rights reserved.