CX3CR1, also known as the fractalkine receptor, is a unique member of the CX3C chemokine receptor family. It specifically binds to its sole ligand, CX3CL1 (fractalkine), to mediate immune cell chemotaxis and adhesion. This receptor plays a crucial role in various physiological and pathological processes, including immune response, neuroinflammation, neurodegenerative diseases, and cancer. The interaction between CX3CR1 and CX3CL1 is highly specific, which presents advantages for drug development targeting this receptor, although no drugs have been successfully marketed yet. Additionally, cholesterol molecules have been found to play a key role in the activation and signal transduction of CX3CR1, influencing its conformation and function. Understanding the molecular mechanisms of CX3CR1 and its ligand recognition provides valuable insights for developing targeted therapies for related diseases.