CD133, also known as Prominin-1, is a pentaspan membrane glycoprotein expressed on the surface of various stem cells and cancer stem cells (CSCs). It plays a crucial role in tumorigenesis, metastasis, recurrence, and drug resistance, and is involved in the regulation of cellular energy metabolism, affecting glucose uptake, autophagy, and ATP synthesis. Moreover, the function of CD133 is not limited to cancer cells; it is also expressed in differentiated cells and stem/progenitor cells in normal tissues and is involved in multiple cellular processes, coordinating signaling pathways that are often deregulated in cancer, such as the PI3K/Akt signaling and Wnt/β-catenin pathways.