Given that malin and laforin form a complex, we decided to test the activity of AbMole Riociguat BAY 63-2521 monomeric and dimeric laforin in the presence of malin using the malachite green assay. Thus, both forms maintain phosphatase activity in the presence of malin. Although there was no change in the ability of monomeric and dimeric laforin to bind malin, we surmised that the binding of malin with laforin could have a differential impact on glucanbinding. To determine how monomeric and dimeric laforin interact with glucans in the presence of malin, we incubated equal amounts of GST-malin-HIS6 with both forms of laforin and then performed the glucan-binding assay as described above. The presence of malin decreased the binding of monomeric laforin to glucans as indicated by the presence of monomeric laforin in both the pellet and supernatant fractions. However, the presence of malin only minimally decreased the binding of dimeric laforin to amylopectin. Thus, the ability of dimeric laforin to bind glucans is not impaired by malin. These data suggest that monomeric laforin binds to malin and that the laforinmalin complex does not bind as tightly to glucans as laforin monomer alone. Defining laforin dimerization is necessary to evaluate the functional and pathological role of laforin in Lafora disease. In the present study, we demonstrate that monomeric laforin is the most abundant form of the phosphatase under normal reduced conditions. Our study also establishes that laforin phosphatase activity is similar for both monomer and dimer species. In addition, monomeric and dimeric laforin exhibit equal ability to associate with malin and bind glucans. However, monomeric laforin has decreased glucan-binding capacity in the presence of malin, while the glucan binding of dimeric laforin is not affected by malin. Another key finding of this study is that oxidative conditions play a key role in both the phosphatase activity and oligomerization of laforin. These results demonstrate that lack of a reducing agent drives laforin oligomerization and abolishes the phosphatase activity of laforin. Conversely, the presence of glycogen did not impact laforin oligomerization, but glycogen did decrease its phosphatase activity. Cumulatively, our data establish that monomeric and dimeric laforin possess similar phosphatase activity, glucan binding, and dimerization is enhanced by increased oxidation and that glucan binding in the presence of malin is decreased for monomeric laforin and not for the dimer. Most primary papers and reviews on Lafora disease have formulated hypotheses with the assumption that mutations inactivating monomeric laforin give rise to Lafora disease. Thus, one of the key reasons to initiate this work was to determine if monomeric laforin possesses phosphatase activity, and if not then to re-assess our understanding of disease mutations. The above results clearly demonstrate that monomeric laforin is the most abundant form of laforin and that it contains full phosphatase activity. The lack of phosphatase activity of monomeric laforin reported by Liu et al. is possibly due to the absence of reducing agents either during purification and/or storage. Hs-laforin, Cm-laforin, and SEX4 all contain a CBM and DSP domain and all belong to the newly discovered class of glucan phosphatases. To define how dimerization affects other glucan phosphatases, we purified both Cm-laforin and SEX4 and tested their pNPP and glucan phosphatase activity.