Figure 1.

The multi-layered physiological roles of creatine transporter 1 (CRT1). The primary function of creatine transporter 1 (CRT1) is to refill cellular creatine reserves, to compensate for its steady degradation (1.7% daily), in end-consumer cells incapable of self-synthesizing sufficient amounts of creatine (i.e., neurons, myocytes, and cardiomyocytes). CRT1 orchestrates creatine flux throughout the body by tuning the amount of creatine extracted from the blood by individual organs. CRT1 plays a key role in providing the brain with creatine, essential to higher cognitive functions. It shifts creatine across tissue barriers like the kidney tubules, the blood-brain barrier (BBB), and the inner blood-retinal barrier. It thus mediates reabsorption of creatine from the primary urine and facilitates the maintenance of cerebral and retinal tissue energetics, respectively. At the placenta, CRT1 takes up creatine, crucial for embryofetal development. It also supports the functioning and integrity of the intestinal barrier, and is an immunoregulator in leukocytes and stabilizes erythrocyte plasma membranes. Cr, creatine; BBB, blood-brain barrier; BCSFB, blood-cerebrospinal fluid barrier; iBRB, inner blood-retinal barrier; GAA, guanidinoacetate; RBC, red blood cell; WBC, white blood cell.