Highlights • Pannexin channels are distributed widely in the brain but their mechanisms of regulation by posttranslational modifications are not well defined. • In this review we discuss known physiology and pathology in the brain mediated by pannexins channels. • Emphasis is place on the significant roles that pannexin phosphorylation by Src family kinases has in channel regulation. Abstract Pannexins form single membrane channels that regulate the passage of ions, small molecules and metabolites between the intra- and extracellular compartments. In the central nervous system, these channels are integrated into numerous signaling cascades that shape brain physiology and pathology. Post-translational modification of pannexins is complex, with phosphorylation emerging as a prominent form of functional regulation. While much is still not known regarding the specific kinases and modified amino acids, recent reports support a role for Src family tyrosine kinases (SFK) in regulating pannexin channel activity. This review outlines the current evidence supporting SFK-dependent pannexin phosphorylation in the CNS and examines the importance of these modifications in the healthy and diseased brain. [ABSTRACT FROM AUTHOR]