Membrane protein MLC1 (MLC1) (MLC1)

Membrane protein MLC1 (MLC1) is a transmembrane protein primarily expressed in brain astrocytes, particularly at the end-feet contacting the blood-brain barrier and the pial membrane (UniProt). It plays a critical role in regulating astrocyte volume and maintaining ion and water homeostasis in the central nervous system, likely by modulating the activity of volume-regulated anion channels (VRAC) and other transporters (PubMed: 22328087, 31209783). Mutations in the MLC1 gene are the primary cause of Megalencephalic leukoencephalopathy with subcortical cysts type 1 (MLC1), a rare leukodystrophy characterized by early-onset macrocephaly, brain edema, and progressive motor deterioration (MedlinePlus, NIH). Beyond its role in this rare genetic disorder, MLC1 has been implicated in neuroinflammatory conditions like Multiple Sclerosis, where it may serve as an autoantigen, and in Glioblastoma, where it promotes tumor cell invasion (News-Medical, PubMed: 33040087). Therapeutic strategies currently under investigation include gene therapy using adeno-associated viruses (AAV) to restore functional MLC1 expression, which has received orphan drug designation from the EMA (IDIBELL, Global Genes). Other approaches focus on pharmacological chaperones to improve protein folding and small molecules to modulate its regulatory effects on astrocyte activation (Alliance MLC, Frontiers in Genetics).

Other names

WKL1KIAA0027LVMMLCVLModulator of VRAC current 1Megalencephalic leukoencephalopathy with subcortical cysts protein 1

Gene replacement therapy to restore functional MLC1 protein expression in astrocytes, thereby normalizing ion and water homeostasis and reducing brain edema.