Laforin glucan phosphatase (EPM2A)

Laforin glucan phosphatase (EPM2A) is a unique, dual-specificity protein phosphatase that contains both a carbohydrate-binding module (CBM) and a phosphatase domain, enabling it to specifically bind and dephosphorylate glycogen and related glucans[1][2][4][5]. This enzymatic activity is critical for proper glycogen metabolism—preventing abnormal phosphorylation, maintaining branching, and ensuring glycogen solubility. Loss-of-function mutations in EPM2A, leading to dysfunctional or absent laforin, result in uncontrolled glycogen phosphorylation and formation of insoluble polyglucosan deposits known as Lafora bodies, which accumulate in neurons and other tissues and are the pathological hallmark of Lafora disease[1][2][3][4][5]. Laforin also interacts with malin (an E3 ubiquitin ligase), forming a protein complex that modulates glycogen metabolism by targeting proteins involved in glycogen synthesis for ubiquitination and degradation[1][3]. Defective laforin leads to neurodegeneration, progressive myoclonus epilepsy (Lafora disease), and potentially affects other tissues, though clinical manifestations are predominantly neurological[3][4]. Laforin may also act as a tumor suppressor, but this function is less well-defined[3]. Currently, no drugs specifically target laforin in clinical use, but genetic testing for EPM2A mutations and histopathological detection of Lafora bodies serve as diagnostic biomarkers for Lafora disease[3].

Other names

LaforinDual-specificity protein phosphatase laforinGlucan phosphataseGlycogen phosphataseLafora PTPaseEpilepsy, progressive myoclonus type 2 proteinLafora disease (laforin)EPM2MELFMELF2LAFPTPaseLDELD

Inhibition or enhancement of phosphatase activity could potentially modify glycogen phosphorylation and prevent Lafora body formation (no approved drugs currently exploit this mechanism)