{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe neutral amino acid transporter SLC6A19 (B₀AT1) is a sodium‐dependent carrier predominantly expressed in the luminal (brush‐border) membranes of renal proximal tubule and intestinal epithelial cells. Its identification as the causative gene in Hartnup disorder highlighted its critical role in mediating the uptake of neutral amino acids, while electrophysiological and tracer studies in expression systems have demonstrated that SLC6A19 transports a broad spectrum of neutral amino acids via a 1:1 sodium co‐transport mechanism, with a preference for large neutral amino acids and complex kinetic properties modulated by membrane potential. Its proper localization in epithelia is essential for efficient absorption and re‐absorption of dietary and filtered amino acids."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its basic transport function, SLC6A19 activity is tightly regulated by a network of accessory proteins and kinases. Its expression and catalytic function at the cell surface are dependent on interactions with proteins such as collectrin and ACE2, which facilitate proper membrane trafficking and stabilization. In addition, serum‐ and glucocorticoid‐inducible kinases (SGK1–3) upregulate SLC6A19 activity by enhancing its plasma membrane insertion and retarding its internalization. Further modulation is achieved via interactions with peptidases like aminopeptidase N that can increase local substrate concentrations and with syntaxin family members that may compete with collectrin for binding, thereby influencing the efficiency of amino acid uptake."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPhysiological studies in animal models have further established the significance of SLC6A19 in whole‐body amino acid homeostasis and metabolic regulation. Mice lacking functional SLC6A19 exhibit generalized neutral aminoaciduria, reduced body weight, blunted insulin secretion, and aberrant activation of nutrient stress signaling pathways, underscoring its vital role in maintaining nutrient balance. In addition, impaired tryptophan absorption via SLC6A19 has been linked to disturbances in NAD metabolism during pregnancy, leading to embryonic growth retardation and specific congenital malformations. Finally, during preimplantation development, SLC6A19 contributes to the uptake of amino acids such as L‐proline, with its deficiency resulting in compromised embryo development."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Robert Kleta, Elisa Romeo, Zorica Ristic, et al. 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