SNX25 (sorting nexin 25) is a multifunctional endosomal sorting protein that regulates intracellular trafficking and signaling through several interconnected mechanisms. Primary Function: SNX25 mediates receptor catabolic processes and modulates autophagic flux through its PX, PXA, and RGS domains 1. Mechanism: SNX25 localizes to endosomes via its PXA domain and controls VAMP8 endocytosis and lipid metabolism 2. It negatively regulates TGF-β signaling by enhancing clathrin-dependent endocytic degradation of TGF-β receptors through the lysosomal pathway 3. Additionally, SNX25 recruits RGS proteins to endosomes in a redox-regulated manner, terminating Gαi/q signaling from endosomes and plasma membrane 4. Disease Relevance: SNX25 expression is elevated in temporal lobe epilepsy patients and animal models, suggesting involvement in epileptogenesis 5. A circRNA-encoded SNX25-215 protein variant promotes radioresistance in hepatocellular carcinoma by facilitating BAG6-mediated DNA damage repair 6. Genetic variants in SNX25 modify age-of-onset in Alzheimer's disease, marking it as a disease modifier 7. Clinical Significance: SNX25 represents a potential therapeutic target for managing radioresistance, neurological disorders, and age-related cognitive decline through modulation of endosomal signaling and autophagy.