Pannexins are a family of integral membrane proteins with distinct 
post-translational modifications, sub-cellular localization and tissue 
distribution. Panx1 is the most studied and best-characterized isoform of this 
gene family. The ubiquitous expression, as well as its function as a major ATP 
release and nucleotide permeation channel, makes Panx1 a primary candidate for 
participating in the pathophysiology of CNS disorders. While many investigations 
revolve around Panx1 functions in health and disease, more recently, details 
started emerging about mechanisms that control Panx1 channel activity. These 
advancements in Panx1 biology have revealed that beyond its classical role as an 
unopposed plasma membrane channel, it participates in alternative pathways 
involving multiple intracellular compartments, protein complexes and a myriad of 
extracellular participants. Here, we review recent progress in our understanding 
of Panx1 at the center of these pathways, highlighting its modulation in a 
context specific manner. This article is part of a Special Issue entitled: Gap 
Junction Proteins edited by Jean Claude Herve.