SNX17/27/31 are known as PX-FERM proteins, a sub-group of the PX superfamily that contain a defining PtdInsP-binding PX domain, and a C-terminal 4.1, ezrin, radixin, moesin (FERM) domain with an atypical tertiary structure []. They are modular peripheralmembrane proteins that act as central scaffolds mediating protein-lipid interactions, cargo binding, and regulatory protein recruitment [].SNX17 is a critical regulator of endosomal recycling of numerous receptors, channels, and other transmembrane proteins. It binds to Asn-Pro-Xaa-Tyr (NPxY) sequences in the cytoplasmic tails of cargo such as LDL receptors and the amyloid precursor protein []. SNX27 is a core component of the SNX27-retromer, a multiprotein complex composed of SNX27, the WASH complex and the retromer complex. It specifically binds and directs sorting of a subset of transmembrane proteins containing a PDZ-binding motif at the C terminus []. Its PDZ domain mediates binding to the retromer complex via direct interaction with VPS26 (VPS26A or VPS26B) [], while its PX domain mediates binding to phosphatidylinositol 3-phosphate (PtdIns(3P)) and localization to early endosome membranes []. SNX31 is a sorting nexin that binds to PtdIns3P-enriched lipids via its N-terminal PX-domain. It also binds to uroplakins [].
