Sorting nexin-27 (SNX27)

Sorting nexin-27 (SNX27) is a unique member of the sorting nexin protein family, characterized by the presence of a phox-homology (PX) domain, a FERM domain, and an N-terminal PDZ domain (unique among sorting nexins). SNX27 functions as a key adaptor in the endosomal protein sorting system: by binding to PDZ-binding motifs in the cytosolic tails of transmembrane cargo proteins, it mediates their interaction with the retromer complex, thereby promoting recycling from endosomes to the plasma membrane and preventing lysosomal degradation. SNX27 is highly expressed in neuronal tissue, regulates critical processes such as synaptic plasticity by controlling AMPA receptor localization, and has been implicated in several neurodevelopmental, neurodegenerative, and oncogenic processes. Its dysfunction is associated with intellectual disability, epilepsy, memory deficits, metabolic regulation disturbances, and may contribute to tumorigenesis by modulating cell surface receptor availability and intracellular signaling pathways.

Other names

SNX27KIAA0488methamphetamine-responsive transcript 1MRT1MY014MGC20471sorting nexin family member 27

No small-molecule drugs with defined mechanisms of action specifically target SNX27; mechanisms described are via modulation of SNX27-mediated recycling of PDZ motif-containing cargoes, affecting surface expression of receptors such as AMPA-type glutamate receptors or β2-adrenergic receptors.