Slc7a9, also known as the solute carrier family 7 member 9, is responsible for the exchange of dibasic amino acids and cystine (influx) for neutral amino acids (efflux). Cystine/cysteine transport by Slc7a9 is related to ferroptosis [1]. It is also one of the genes associated with cystinuria, a heritable disorder affecting the cysteine reabsorption by the renal system as well as the reabsorption of dibasic amino acids [2,4,5,6]. Genetic models, such as gene knockout mouse models, can be used to study its functions [3].

In gastric cancer, knockdown of Slc7a9 in cell lines and in patient-derived organoids (PDO), immunocompetent MFC mice allograft models and patient-derived xenograft (PDX) models suppressed cell proliferation, increased chemotherapy sensitivity, reduced cystine transport into cells, hampered intracellular cystine and GSH metabolic flow, decreased GSH synthesis, and increased lipid ROS levels, suggesting that Slc7a9 promotes gastric cancer progression by acting as a suppressor of ferroptosis [1]. In the Slc7a9-/-mouse model of cystinuria, the antioxidant l-Ergothioneine was able to prevent cystine lithiasis by increasing urinary cystine solubility and recovering renal GSH metabolism and mitochondrial function [3].

In conclusion, Slc7a9 plays a crucial role in cystine and amino acid transport, which is associated with ferroptosis and cystinuria. Studies using Slc7a9 knockout mouse models have revealed its functions in promoting cancer progression and in the pathogenesis of cystinuria, providing insights into potential therapeutic strategies for gastric cancer and cystinuria.