Sodium/bile acid cotransporters are integral membrane glycoproteins. Two homologous transporters are involved in the reabsorption of bile acids, one absorbing from the intestinal lumen, the bile duct, and the kidney with an apical localization (SLC10A2;), and the other being found in the basolateral membranes of hepatocytes (SLC10A1). SLC10A1 contains an exoplasmic N terminus, an odd number of transmembrane regions, and a cytoplasmic C terminus. Alanine insertion experiments confirmed that 7 of the 9 hydrophobic stretches are membrane-integrated, with secondary structures and transport activity sensitive to positional displacement. Two amphipathic sequences are critical for intramolecular interactions and for proper trafficking of SLC10A1 to the plasma membrane.