NHL repeat containing E3 ubiquitin-protein ligase 1 (NHLRC1)

NHL repeat containing E3 ubiquitin-protein ligase 1 (NHLRC1), commonly called malin, is an intracellular RING-finger E3 ubiquitin ligase characterized by multiple NHL repeats[4]. Malin functions as part of the ubiquitin-proteasome system and forms a complex with the phosphatase laforin (encoded by EPM2A) to regulate the breakdown of misfolded and excess proteins, and more specifically to control glycogen metabolism in neurons and other tissues[1][3]. Mutations in NHLRC1 lead to Lafora disease (progressive myoclonus epilepsy type 2), a fatal neurodegenerative disorder marked by epileptic seizures and progressive cognitive and motor decline, primarily due to abnormal glycogen (polyglucosan) accumulation in neurons resulting from impaired protein quality control and degradation[1][3][4].

Other names

malinEPM2BbA204B7.2NHL repeat-containing protein 1RING-type E3 ubiquitin transferase NHLRC1NHLC1_HUMANMGC119262MGC119264MGC119265

Drugs targeting E3 ubiquitin ligases would generally act by modulating protein degradation pathways, either inhibiting or enhancing ubiquitination activity; however, no drugs directly targeting NHLRC1/malin are currently known[2].