Slc7a9, encoding the protein bo,+AT, is responsible for the exchange of dibasic amino acids and cystine (influx) for neutral amino acids (efflux), with cystine/cysteine transport related to ferroptosis [1]. It is also involved in the b0,+ transporter system along with SLC3A1, and mutations in Slc7a9 are associated with cystinuria, a heritable disorder affecting cysteine and dibasic amino acid reabsorption [4,5,6,7,8].

In gastric cancer, Slc7a9 knockdown suppressed cell proliferation, increased chemotherapy sensitivity, and reduced cystine transport, GSH synthesis, and increased lipid ROS levels, promoting ferroptosis [1]. In esophageal squamous cell carcinoma (ESCC), knockdown of Slc7a9 significantly suppressed cell proliferation, invasion, and migration, while overexpression enhanced these processes. High Slc7a9 expression in ESCC tissues was associated with lymph node metastasis and poor survival [2]. In the Slc7a9 -/- mouse model of cystinuria, l-Ergothioneine treatment prevented cystine lithiasis by increasing urinary cystine solubility and restoring renal GSH metabolism and mitochondrial function [3].

In conclusion, Slc7a9 plays crucial roles in amino acid transport, ferroptosis regulation, and cancer cell behavior. The study of Slc7a9, especially through gene-knockout mouse models, has provided insights into its functions in diseases like gastric cancer, ESCC, and cystinuria, offering potential targets for treatment strategies.