SLC16A12 functions primarily as a creatine and guanidinoacetate transporter that is critical for creatine homeostasis in multiple tissues 1. The transporter mediates creatine and guanidinoacetate transport independent of membrane potential and extracellular Na+, Cl-, or pH 1. In the kidney, SLC16A12 localizes to the basolateral membrane of proximal tubules where it is essential for reabsorption of creatine and guanidinoacetate from urine 1. Loss of SLC16A12 function results in decreased plasma levels and increased urinary excretion of both creatine and guanidinoacetate 1. The transporter shows continuous creatine efflux activity, contrasting with the controlled release mediated by other creatine transporters like SLC22A15 2. Disease relevance includes association with juvenile cataracts, microcornea, and glucosuria in humans carrying heterozygous mutations 1. In clear cell renal cell carcinoma, decreased SLC16A12 expression correlates with poor prognosis and serves as an independent prognostic factor 3. The gene also shows differential methylation patterns associated with maternal folate levels during pregnancy 4 and is involved in various cancer-related processes through epigenetic modifications 56.