CX3CR1 is a G protein-coupled chemokine receptor that functions as a key regulator of immune cell migration and neuroinflammation. The receptor binds fractalkine (CX3CL1), a chemokine produced by neurons, and is primarily expressed on microglial cells and specific T cell populations in the central nervous system 1. CX3CR1 also marks distinct differentiation states of human and murine CD8+ and CD4+ T cells, with graded expression correlating to functional properties including migratory capacity 2. Mechanistically, CX3CR1 activation by fractalkine promotes M2 microglial polarization and attenuates neuroinflammation through the AMPK/PPARγ signaling pathway, enhancing hematoma clearance and improving neurological outcomes 3. The receptor is essential for microglial development, as CD14/CX3CR1+ myeloid progenitors differentiate into ramified microglia with proper phagocytic function 4. Clinically, CX3CR1 dysfunction contributes to multiple pathologies. Deficiency of CX3CR1+ effector T and NK cells occurs in biliary atresia, a severe infantile cholangiopathy 5. In neurodegenerative contexts, elevated neuronal cathepsin S increases neuroinflammation via CX3CL1-CX3CR1 axis activation, promoting cognitive decline in aging and Alzheimer's disease 6. Additionally, CX3CR1+ transitional macrophages accumulate in pulmonary fibrosis and support fibrotic responses 7. CX3CR1 thus represents a promising therapeutic target for neuroinflammatory and fibrotic diseases.