Phox (PX) domain-containing sorting nexins (SNXs) are emerging as important 
regulators of endocytic trafficking. Sorting nexin 27 (SNX27) is unique, as it 
contains a PDZ (Psd-95/Dlg/ZO1) domain. We show here that SNX27 is primarily 
targeted to the early endosome by interaction of its PX domain with PtdIns(3)P. 
Although targeted ablation of the SNX27 gene in mice did not significantly 
affect growth and survival during embryonic development, SNX27 plays an 
essential role in postnatal growth and survival. N-Methyl-d-aspartate (NMDA) 
receptor 2C (NR2C) was identified as a novel SNX27-interacting protein, and this 
interaction is mediated by the PDZ domain of SNX27 and the C-terminal 
PDZ-binding motif of NR2C. Increased NR2C expression levels, together with 
impaired NR2C endocytosis in SNX27(-/-) neurons, indicate that SNX27 may 
function to regulate endocytosis and/or endosomal sorting of NR2C. This is 
consistent with a role of SNX27 as a general regulator for sorting of membrane 
proteins containing a PDZ-binding motif, and its absence may alter the 
trafficking of these proteins, leading to growth and survival defects.