SNX27 belongs to a family of endosomal sorting proteins, defined by the presence of a phox-homology (PX) domain, which binds phosphatidylinositol-3-monophosphate (PI3P) in the early endosome (EE) (Cullen and Korswagen, 2011). Of the ~33 sorting nexins described to date, SNX27 is unique because it is the only sorting nexin that contains a PDZ (post synaptic density (PSD)-95, discs large, zona occludens) domain. We showed previously that the PDZ domain of SNX27 associates directly with the C-terminal PDZ binding motif in GIRK2c/GIRK3 subunits (Balana et al., 2011; Lunn et al., 2007). In heterologous expression systems and hippocampal neurons, overexpression of SNX27 reduces the amplitude of GABABR-activated GIRK currents (Balana et al., 2011; Lunn et al., 2007) and in rodent neocortex, RNA expression is regulated by psychostimulant exposure (Kajii et al., 2003). SNX27 also regulates other signaling proteins, including glutamate receptors (Wang et al., 2013), 5-HT receptors (Joubert et al., 2004), multidrug resistance-associated protein 4 (Hayashi et al., 2012) and β2 adrenergic receptors (Lauffer et al., 2010). For β2 adrenergic receptors, knockdown of SNX27 by RNAi in cultured aortic smooth muscle cells
