SLC6A8 encodes a creatine:sodium symporter that mediates the cellular uptake of creatine, playing a crucial role in cellular energy metabolism 12. The transporter facilitates creatine import across cell membranes in a sodium-dependent manner, enabling cells to utilize creatine for ATP generation through the phosphocreatine system 13. In cancer contexts, SLC6A8 exhibits complex roles: it supports tumor growth by facilitating creatine uptake for energy production 23, yet creatine can also induce ferroptosis through ERK2-FSP1 signaling pathway modulation 4. The transporter is particularly important in metastatic colonization, where it enables uptake of extracellularly produced phosphocreatine to fuel ATP generation during hypoxic stress 1. SLC6A8 also regulates immune cell function, with creatine uptake reprogramming macrophage polarization by modulating cytokine responses 5. Clinically, SLC6A8 represents both a therapeutic target and biomarker - its inhibition shows anti-tumor effects in colorectal cancer models 2, while knockout suppresses hepatocellular carcinoma invasion and migration 6. The gene is associated with cerebral creatine deficiency syndrome 1 when mutated, highlighting its essential role in brain creatine transport.