MAGE family member L2 (MAGEL2)

MAGE family member L2 (MAGEL2) is a large, brain-enriched, maternally imprinted and paternally expressed protein of the MAGE (melanoma-associated antigen) family[7]. It functions as a regulator of E3 ubiquitin ligases, particularly as part of the MUST (MAGEL2–USP7–TRIM27) complex, facilitating endosomal protein recycling through modulation of ubiquitination and actin-dependent pathways[1][6][7]. MAGEL2 is essential for trafficking of membrane proteins such as AMPA receptors and is highly expressed in the hypothalamus, where it regulates hormone secretion (oxytocin, vasopressin, somatostatin, TSH, somatotropin, and LH), synaptic transmission, neurotransmitter balance, and developmental processes[1][2][6][7]. Disruption or deletion of MAGEL2 causes the neurological and developmental syndromes Prader-Willi syndrome and Schaaf-Yang syndrome, both of which display neurobehavioral, metabolic, and endocrine abnormalities[2][6][7]. At the molecular level, MAGEL2 also regulates mRNA processing and phase separation phenomena in the cytoplasm, and pathological mutations can cause protein mislocalization to the nucleus, correlating with disease severity[2][3][5]. Currently, no targeted therapies or drugs are known to modulate MAGEL2 function directly.

Other names

MAGE-like protein 2NDNL1nM15Necdin-like protein 1Protein nM15PWLSSHFYNGmelanoma antigen family L2necdin-like protein 1

null (No approved drugs target MAGEL2 directly as of this data. Mechanistic modulation primarily relates to gene dosage or loss-of-function.)