VPS35-Retromer: Multifunctional Roles in Various Biological Processes – A Focus on Neurodegenerative Diseases and Cancer

The Vacuolar Protein Sorting 35 (VPS35)-Retromer complex plays a crucial role in intracellular protein trafficking and recycling, ensuring the proper transport of membrane protein receptors to the trans-Golgi network. By preventing lysosomal degradation, VPS35 helps maintain the functionality of transmembrane proteins, thereby supporting essential cellular processes.

Beyond its role in protein sorting, VPS35 is deeply involved in autophagy, mitophagy, and mitochondrial homeostasis, regulating vital functions such as epidermal regeneration, neuronal iron homeostasis, and synaptic activity. Dysfunction in VPS35 has been linked to significant neuronal impairments, contributing to the pathogenesis of neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease. Studies have demonstrated that disruptions in the Retromer complex compromise neuronal survival, exacerbating disease progression.

In addition to its neurological implications, VPS35 plays a role in cancer biology, influencing tumor growth and metastasis in liver and breast cancer by modulating multiple signaling pathways. Given its broad impact on cellular health, PF-4708671 VPS35 presents itself as a compelling therapeutic target for neurodegenerative diseases and cancer treatment. Further exploration of VPS35-targeting strategies may unlock new possibilities for clinical intervention, providing hope for more effective disease management in these fields.