“…Such an example is found in a mouse model of Krabbe's disease, the twitcher mouse, in which toxic accumulation of galactosylsphingosine (psychosine) disrupts lipid rafts, resulting in the inhibition of survival signals such as PKC, Akt, and ERK; defects in axonal transport and synaptic maintenance; and neuronal degeneration through a dying‐back mechanism (White et al, ; Castelvetri et al, ; Cantuti Castelvetri et al, ; Hawkins‐Salsbury et al, ; Teixeira et al, ; Cantuti‐Castelvetri et al, ). Glucosylceramide accumulation in Gaucher's disease (Hattersley et al, ), sulfatide accumulation in metachromatic leukodystrophy (Moyano et al, ), globotriaosylceramide accumulation in Fabry's disease (Labilloy et al, ), and cholesterol accumulation in Niemann‐Pick type C (Vainio et al, ) also preferentially take place in lipid rafts and cause altered lipid raft dynamics. Therefore, it is conceivable that they involve neuronal vulnerability through a similar mechanism that includes membrane disruption as a root cause for downregulation of survival signals leading to neurodegeneration.…”