The above results clearly demonstrate that Abmole Cycloheximide 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. Similar to Hslaforin, SEX4 and Cm-laforin both formed dimers. Contrary to what we observed for Hs-laforin, the phosphatase activity of the monomeric SEX4 and Cm-laforin was higher than the dimeric form. These data indicate that glucan phosphatases are functional in their monomeric state, but that differences are present across Kingdoms. Our results from cell Publications Using Abomle AZ960 culture suggest that laforin dimerization may be a dynamic process. The sensitivity of the oligomericmonomeric transition to the presence of reducing agents indicates that inter-molecular Cys-Cys bridges play a key role in oligomer formation. These data suggests that laforin is present in vivo as a combination of monomeric and oligomeric forms, and changes in the cellular reducing conditions may regulate the transition from one state to the other. In support of this hypothesis, a recent paper found that a laforin mutation, laforin-Ser25Ala, is unable to interact with itself in both a yeast two-hybrid system and in mammalian cell culture experiments. We found that both monomeric and dimeric laforin bind glucans with equal affinity. This finding suggests that sites involved in laforin dimerization do not affect the conformation of essential CBM residues involved in glucan-binding. Next, we analyzed the inhibitory role of glycogen on laforin phosphatase activity. We observed that this inhibitory role is not due to alterations in the oligomeric-monomeric transition, as the presence of glycogen did not affect oligomer formation. Moreover, a dual specificity phosphatase lacking a carbohydrate-binding domain (VHR) was resistant to glycogen inhibition.