SNX27 (sorting nexin 27) is a metazoan-specific endosomal adaptor protein that plays a critical role in retrograde transport from endosomes to the plasma membrane, promoting recycling of internalized transmembrane proteins 1. SNX27 is unique among sorting nexins as it contains both a PX domain and a PDZ domain, enabling it to bind specifically to transmembrane proteins containing C-terminal PDZ-binding motifs 2. The protein associates with the retromer complex to prevent cargo entry into the lysosomal degradation pathway and promotes retromer-tubule based plasma membrane recycling 1. Over 100 cell surface proteins have been identified as binding partners of the SNX27-retromer complex 2. SNX27 also interacts with the WASH complex through FAM21 subunit binding, which nucleates actin filaments to establish endosomal recycling domains 3. In neurons, SNX27 is particularly important for trafficking glutamate receptors and synaptic proteins, with overexpression enhancing synaptic transmission and cognitive function 4. The protein regulates AMPA receptor trafficking both directly and indirectly through sorting of the synaptic adhesion molecule LRFN2 5. Additionally, SNX27 functions in immune cell polarization, translocating to the immunological synapse and interacting with diacylglycerol kinase ζ to modulate T-cell activation 6. Dysregulation of SNX27 is linked to neurological diseases including Down syndrome and Alzheimer's disease 1.