Laforin (LDE)

Laforin contains a dual specificity phosphatase domain (DSP) and a carbohydrate binding module subtype 20 Its physiological substrate has yet to be identified and the molecular mechanisms in which mutated laforin causes Lafora disease is unknown.Biochemical, immunofluorescence, and ultrastructural studies on transfected HeLa cells revealed that laforin is a cytoplasmic protein associated with polyribosomes. Expression of 2 proteins with missense mutations seen in EPM2A patients resulted in ubiquitin-positive perinuclear aggregates, suggesting that these were misfolded proteins targeted for degradation. laforin is involved in translational regulation and that protein misfolding may be one of the molecular bases of the Lafora disease phenotype caused by missense mutations in the EPM2A gene.