Slc6a14, also known as amino acid transporter B0,+ (ATB0,+), is a Na+/Cl--coupled transporter for multiple amino acids, including glutamine, serine, glycine, and methionine. It drives the glutaminolysis and serine-glycine-one-carbon pathways in cancer, which are crucial for cancer cell growth and proliferation. It also has a role in the import and concentration of neutral and cationic amino acids into the cytoplasm of different cell types, and thus is important in various physiological and pathophysiological processes [3,4].

In ulcerative colitis (UC), SLC6A14 knockdown markedly suppressed ferroptosis and pyroptosis. RNA sequencing showed it inhibited the expression of PAK6, and ChIP and Western blot analysis demonstrated it negatively regulated PAK6 expression in a C/EBPβ-dependent manner. In cystic fibrosis, it may modulate the anti-infective response and epithelial integrity of the airways. Slc6a14-/-mice on a high-fat diet gained more weight, developed fatty liver and metabolic syndrome, indicating a link between its deficiency and obesity under such dietary conditions. In breast cancer, SLC6A14 is upregulated in estrogen receptor positive cells, and inhibition of HSP90β, which interacts with SLC6A14, decreased its transport activity and level at the cell surface [1,2,5,6,7].

In conclusion, Slc6a14 plays essential roles in multiple biological processes, especially in amino acid-related metabolic pathways. Its functions are implicated in diseases such as ulcerative colitis, cystic fibrosis, obesity-related metabolic syndrome, and breast cancer. Studies using knockout mouse models have provided valuable insights into its role in these disease conditions, helping to understand the underlying mechanisms and potentially guiding the development of new therapeutic strategies.