Psychosine or galactosylsphingosine is an intermediate involved in the catabolism of monoglycosylceramides. It is primarily produced through the galactosylation of sphingosine and is present only in very low levels in normal tissue. Krabbe disease (KD) or globoid cell leukodystrophy (GLD) is an inherited autosomal recessive lysosomal storage disease in which the loss of function of the lysosomal enzyme b-galactosylceramidase (GALC) leads to progressive accumulation of undigested galactosylsphingolipids and severe neurodegeneration characterized by loss of oligodendroglial cells, extensive demyelination in the nervous system and the appearance of distinctive multinucleate globoid cells in the white matter. The purpose of this research was to study the associated signals to the progressive psychosine accumulation, that may lead to disruption of lipid rafts (LRs). LRs are defined as unique regions of the cell membrane that have a characteristically high concentration of cholesterol and sphingolipids. The abnormal accumulation of psychosine may introduce architectural and functional changes in these domains, leading to cellular dysfunction, brain deterioration and irreversible neurological handicap in the incurable KD. Our results demonstrated that the accumulation of psychosine is accompanied by changes in the distribution of the LR markers flotillin-2 and caveolin-1 associated to an increase of PDCD4.