Transport and inhibition mechanisms of human creatine transporter

Parent Summary: This study reveals the 3D structure of the creatine transporter (CRT). The research team used high-resolution imaging to understand how CRT works at the atomic level, showing how creatine binds to CRT and how key elements like sodium and chloride ions help this process. They identified which specific parts of the transporter are essential for its function and how changes in these parts lead to disease. They also studied a drug called RGX-202, now in clinical trials for cancer, and found that it blocks creatine from entering cells by mimicking its shape and taking its place. This helps explain how certain mutations cause CRT to stop working and gives researchers a clearer map for designing future treatments. This paper provides the first detailed picture of CRT in action and shows exactly how creatine and its blockers interact with it. This information may help scientists design better treatments for creatine transporter deficiency and guide future drug development.

Link to article: https://www.nature.com/articles/s41421-025-00801-4

PubMed:  https://pubmed.ncbi.nlm.nih.gov/40325013/

Authors: Jiahui Chen, Yimin Zhang, Nanhao Chen, Jingpeng Ge & Jie Yu

Key Terms: CTD, Basic Science, Mutation Study, In vitro