Malin (E3 ubiquitin-protein ligase NHLRC1) (NHLRC1)

Malin, encoded by the NHLRC1 (also known as EPM2B) gene, is an E3 ubiquitin-protein ligase that plays a critical role in regulating glycogen metabolism within the central nervous system. It works in complex with the phosphatase laforin to monitor glycogen chain length and facilitate the degradation of proteins involved in glycogen synthesis, such as glycogen synthase and protein targeting to glycogen (PTG). Mutations in the NHLRC1 gene lead to Lafora disease, a fatal, progressive myoclonus epilepsy characterized by the accumulation of insoluble, poorly branched glycogen aggregates known as Lafora bodies in neurons and other tissues. TSHA-121 is an investigational adeno-associated virus (AAV) gene therapy developed to deliver a functional version of the NHLRC1 gene directly to CNS cells. By restoring malin function, the therapy aims to halt the formation of toxic polyglucosans and mitigate the neurodegenerative progression of the disease.

Other names

E3 ubiquitin-protein ligase NHLRC1NHL repeat-containing protein 1EPM2BMalin

Gene replacement therapy designed to deliver a functional copy of the NHLRC1 gene to CNS cells to restore malin protein activity and prevent the accumulation of toxic polyglucosans.