The interaction of amino acid transporters with accessory proteins guarantees their insertion in the membrane and may modulate the activity or the supply of substrate. Neutral amino acid transporters of the SLC6 family have been shown to rely on the expression of Tmem27 and the angiotensin-converting enzyme 2 (ACE2), two members of the renin-angiotensin system (RAS). ACE2 and Tmem27’s role as a partner protein of amino acid transporters was revealed by gene ablation and co-expression in heterologous system. The tmem27 knock-out mice presented generalized neutral aminoaciduria, while ace2 knock-out animal had normal amino acids excretion. The amino acid transport in the kidneys of tmem27 and intestine of ace2 knock-out animals is reduced, moreover Slc6 family amino acid transporters expression is affected. In the kidney of tmem27 mice the expression of B0AT1, B0AT3 (Slc6a19 and 18) and the imino transporter SIT1 (Slc6a20) were abolished or strongly reduced. In the ace2 knock-out mice the renal expression of B0AT1 was normal, while it was absent in the small intestine. B0AT1 is the major neutral amino acid transporter in the kidney and intestine, and has two tissue specific accessory proteins, Tmem27 in the kidney and ACE2 in intestine. Mutations in the gene (SLC6A19) encoding the B0AT1, but not in the genes encoding the accessory proteins, are the cause of Hartnup disorder. Hartnup disorder patients present aminoaciduria, and may also additionally develop symptoms resembling pellagra, including light-sensitive dermatitis and diarrhea that manifests under conditions of stress and malnutrition. Pellagra like symptoms is thought to result from defective intestinal absorption of L-tryptophan, the precursor of niacin. The ablation of B0AT1 in the intestine of ace2 knock-out mice leads to a decreased L-tryptophan absorption, increased susceptibility to intestinal infection, but not to dermatitis-like symptoms. These results suggest that B0AT1 ablation in intestine may contribute to the development of symptoms different from aminoaciduria observed in the Hartnup disorder subjects. The phenotype of Hartnup patients has been shown to vary due to nutritional status, environment, and high frequency of compound heterozygous. Additionally, mutated transporter can interact differentially with tissue specific accessory proteins, and might contribute to the phenotypic heterogeneity among individuals with Hartnup disorder. The work on amino acid transporters of the SLC6 family and their tissue-specific partner proteins has provided critical information concerning the modulation of amino acid transporter function, however several questions are still waiting to be solved such as the mechanism guiding the selection of the partner protein in kidney, regulation of the expression and function of the transporters and their accessory proteins by diet, gender, hormones, age and diseases are crucial and are just starting to be investigated.