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The P2X4 receptor (P2X4) is an ATP-gated cation channel that is highly permeable to Ca2+ and widely expressed in neuronal and glial cell types throughout the central nervous system (CNS).A growing body of evidence indicates that P2X4 plays key roles in numerous central disorders.P2X4 trafficking is highly regulated and consequently in normal situations,P2X4 is present on the plasma membrane at low density and found mostly within intracellular endosomal/lysosomal compartments.An increase in the de novo expression and/or surface density of P2X4 has been observed in microglia and/or neurons during pathological states.This review aims to summarize knowledge on P2X4 functions in CNS disorders and provide some insights into the relative contributions of neuronal and glial P2X4 in pathological contexts.However,determination of the cell-specific functions of P2X4 along with its intracellular and cell surface roles remain to be elucidated before its potential as a therapeutic target in multiple disorders can be defined.