Thus, an alteration of the capacity of GNE to effectively regulate GM3 synthesis could alter progressively the ability of muscle cells to adapt to their environment or to cope with their needs. To date, no investigation has been made to determine a relation between the ganglioside synthesis regulated by GNE and HIBM. Ganglioside GM3 is Danshensu particularly abundant in the kidney tissues. Sialic acids are indeed important in kidneys, since their physicochemical properties are involved in the maintenance of the filtration barrier of glomeruli. More particularly, changes in ganglioside expression in these organs is implicated in the pathogenesis of proteinuria. More Trifolirhizin recently, it was demonstrated that alteration of ganglioside GM3 levels in kidneys can be related to glomerular hypertrophy and proteinuria. One of the main problems when one tries to unravel the molecular and cellular pathways of HIBM is the lack of human muscle samples. The rough lack in GM3 ganglioside in GneM712T/M712T mice could have very well explained part of the renal pathologies observed in these animals, according to the relative abundance of GM3 in the kidney tissues. Moreover, it was previously demonstrated that alteration of ganglioside GM3 levels in kidneys can lead to glomerular hypertrophy and proteinuria. The present work emphasizes the fact that GNE is a moonlighting enzyme, capable of multiple intracellular roles, roles that only recent studies were able to discover. The relationship between mutations of GNE and cellular levels of gangliosides was never explored before. Our results demonstrate that, beyond the production of sialic acid, the synthesis of specific molecules such as gangliosides, could be affected. Among gangliosides, GM3 is of particular interest, due to its preponderance in muscles. Thus, an alteration of GM3 levels in HIBM cells could lead to a variety of detrimental effects and modification of cell metabolism and draw a bridge between several past observations on HIBM cells such as impairment of myogenic terminal differentiation or modification of the apoptotic signaling pathways as GM3 is precisely involved in terminal differentiation of myoblasts and the control of apoptosis.