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Updated: Jun 17, 2026

High-Throughput Expression and Purification of Human Solute Carriers for Structural and Biochemical Studies
Published on: September 29, 2023
Targeting the creatine transporter SLC6A8: Mechanisms and emerging therapeutic strategies for multiple diseases
Kai Wang1, Chenjie Liu1, Jinkang He1
1Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences &Peking Union Medical College, Nanjing, China.
Abstract:
Solute carrier family 6 member 8 (SLC6A8) is a Na+- and Cl--dependent creatine transporter that mediates the transmembrane uptake of creatine, thereby sustaining intracellular creatine pools and cellular energy homeostasis. Dysregulated expression and function of SLC6A8 have been linked to creatine transporter deficiency (CTD), multiple malignancies, diabetes, obesity, and heart failure, underscoring its promising potential as a therapeutic target. Conventional creatine supplementation yields limited therapeutic benefit in the majority of CTD patients. Nevertheless, emerging strategies including gene therapy, small-molecule correctors, and lipophilic prodrug approaches have demonstrated preliminary efficacy in preclinical models of CTD. SLC6A8 is aberrantly expressed across numerous cancer types, and its inhibitor RGX-202 (also termed ompenaclid, chemically identified as β-GPA) exerts broad antitumor activity in preclinical models of colorectal cancer and hepatocellular carcinoma. This review summarizes recent advances delineating the involvement of SLC6A8 in neurological disorders, cancer, and other pathological conditions, with a particular emphasis on its translational potential as a therapeutic target. Clarifying the research status of SLC6A8 in various systemic diseases enables subsequent researchers to comprehensively understand its biological functions and clinical translational value from a more systematic perspective.
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