Plays an important role in amino acid transport by acting as binding partner of amino acid transporters SLC6A18 and SLC6A19, regulating their trafficking on the cell surface and their activity (PubMed:17167413, PubMed:16985211). May also play a role in trafficking of amino acid transporters SLC3A1 and SLC7A9 to the renal cortical cell membrane (PubMed:16985211). Regulator of SNARE complex function (PubMed:16330323). Stimulator of beta cell replication (PubMed:16330324). Monomer (PubMed:16330324). Homodimer (PubMed:16330324). Homodimer; dimerization prevents CLTRN cleavage by BACE2 (PubMed:16330324). Interacts with SNAPIN (PubMed:16330323). Interacts with SLC6A18; this interaction regulates the trafficking of SLC6A18 to the cell membrane and its amino acid transporter activity (PubMed:17167413, PubMed:19478081). Interacts with SLC6A19; this interaction regulates the trafficking of SLC6A19 to the cell membrane and its amino acid transporter activity (PubMed:17167413). Interacts with SLC6A20B (PubMed:17167413). Localizes to the brush border membranes of cells in the proximal tubules of kidney (PubMed:17167413). Colocalizes with SLC6A19 in the early proximal S1 tubule (PubMed:17167413). Expressed on the apical surface of the proximal tubules in the renal cortex (at protein level) (PubMed:16985211). Kidney; collecting ducts and proximal tubule (PubMed:11278314, PubMed:17167413, PubMed:16985211). Pancreas; beta cells of islets (PubMed:16330323, PubMed:16330324). Up-regulated by high glucose concentration in beta-cells (at protein level). The cleavage site containing the double Phe-Phe motif acts as negative regulator of shedding by BACE2. Glycosylated. Glycosylation is required for plasma membrane localization and for its cleavage by BACE2. Proteolytically processed in pancreatic beta cells by BACE2 leading to the generation and extracellular release of soluble CLTRN, and a corresponding cell-associated C-terminal fragment which is later cleaved by gamma-secretase (PubMed:16330324, PubMed:21907142). This shedding process inactivates CLTRN (PubMed:16330324). Three cleavage sites have been identified for BACE2, two clustered sites after Phe-116 and Leu-118 and a more membrane proximal site at Phe-125; the preferred BACE2 cleavage site seems to be between Phe-125 and Leu-126, Phe-116 and Leu-118 act as alternative sites (By similarity). Deficient mice are viable and fertile but exhibit a severe defect in renal amino acid uptake due to down-regulation of apical amino acid transporters in the kidney (PubMed:17167413). Greater urine output, more dilute urine, a defect in urinary concentration, higher osmolar clearance and an increase in free water absorption, suggesting an osmotic diuresis (PubMed:16985211). Decreased urine osmolytes sodium and urea, presence of tyrosine and glutamine crystals in the urine, and increased excretion of amino acids in the urine, suggesting an aminoaciduria (PubMed:16985211). Decreased population of amino acid transporters SLC6A19, SLC3A1 and SLC7A9 in the renal cortical cell membrane (PubMed:16985211). Increased intracellular SLC1A1 levels (PubMed:16985211). Belongs to the CLTRN family.