The multi-tasked life of GM1 ganglioside, a true factotum of nature

• GM1 is ubiquitous in vertebrate tissues with numerous functional activities.
• GM1 is functionally prominent in lipid microdomains.
• GM1 modulates neurotrophic activities through association with receptors.
• GM1 mediates transport of Ca2+, Na+, and K+ via ion channels and exchangers.
• GM1 mediates the activity of effector T cells in the immune system.
• GM1 has therapeutic potential in treatment of neurodegenerative diseases.

GM1 ganglioside occurs widely in vertebrate tissues, where it exhibits many essential functions, both in the plasma membrane and intracellular loci. Its essentiality is revealed in the dire consequences resulting from genetic deletion. This derives from its key roles in several signalosome systems, characteristically located in membrane rafts, where it associates with specific proteins that have glycolipid-binding domains. Thus, GM1 interacts with proteins that modulate mechanisms such as ion transport, neuronal differentiation, G protein-coupled receptors (GPCRs), immune system reactivities, and neuroprotective signaling. The latter occurs through intimate association with neurotrophin receptors, which has relevance to the etiopathogenesis of neurodegenerative diseases and potential therapies. Here, we review the current state of knowledge of these GM1-associated mechanisms.