SNX21 (sorting nexin family member 21) is a membrane-associated scaffolding protein that functions in endosomal trafficking and protein organization. Primary Function: SNX21 contains a phosphatidylinositol 3-phosphate (PtdIns(3)P) binding PX domain and binds to phosphatidylinositol 4,5-bisphosphate-enriched membranes 1, localizing to early endosome membranes where it regulates receptor degradative sorting 2. Mechanism: SNX21 functions as an endosomal scaffold through distinct protein interaction domains: its N-terminal extension recruits huntingtin (Htt), while its PXB domain associates with septins, a family of cytoskeletal and membrane-associated proteins 3. This dual-binding capacity enables SNX21 to coordinate endosomal organization and facilitate movement of internalized vesicles into early endosomes 2. Disease Relevance: SNX21 appears to regulate the IL-22-STAT3-CCL20 pathway, as it was identified as a potential target of miR-26, a tumor suppressor dysregulated in cutaneous T-cell lymphoma 4. Additionally, SNX21 expression is regulated by MMP gene variants associated with hypertension development 5. Clinical Significance: Given SNX21's role in receptor trafficking and its association with disease-related regulatory pathways, modulating SNX21 function may have therapeutic implications for lymphomas and metabolic disorders, though further mechanistic studies are needed.