VPS29 is a core component of multiple endosomal sorting complexes that regulate cargo recycling and retrograde transport. As part of the retromer complex, VPS29 associates with VPS26 and VPS35 to form a cargo-recognition trimer that mediates retrograde transport of transmembrane cargo from endosomes to the trans-Golgi network 1. VPS29 also functions as a central scaffold protein in the Retriever complex, where it associates with DSCR3 and C16orf62 to form a heterotrimer that promotes cell surface recycling of proteins like α5β1 integrin through a retromer-independent pathway 2. The protein serves as a key coordinator in the Commander complex, which is required for endosomal recycling and is mutated in Ritscher-Schinzel syndrome 3. VPS29 coordinates physical assembly of retrieval complexes with regulatory components, establishing distinct retrieval stations for endosomal sorting 4. Beyond trafficking functions, VPS29 has been identified as a genetic modifier of tau propagation in tauopathies 5 and shows clinical relevance as a prognostic biomarker in hepatocellular carcinoma, where overexpression correlates with poor patient outcomes 6. The protein's structure includes a phosphoesterase fold that enables its diverse protein-protein interactions 1.