Major facilitator superfamily domain-containing protein 8 (MFSD8) (MFSD8)

Major facilitator superfamily domain-containing protein 8 (MFSD8), also known as CLN7, is a multi-pass membrane protein primarily localized to the lysosomal membrane (UniProt: Q8NHS3). It belongs to the major facilitator superfamily (MFS), suggesting a role in the transport of small solutes, although its specific physiological substrate is still being characterized (PubMed: 17617514). MFSD8 is critical for lysosomal function, and its deficiency leads to the accumulation of storage material and impaired autophagy. Mutations in the MFSD8 gene cause Neuronal Ceroid Lipofuscinosis 7 (CLN7), a form of Batten disease characterized by progressive neurodegeneration, epilepsy, and vision loss in children (NIH: GARD). Because the disease results from a loss-of-function mutation, MFSD8 is a primary target for gene replacement therapies. Experimental treatments, such as AAV-based gene delivery (e.g., TSHA-118), aim to restore lysosomal transport activity and halt disease progression (ClinicalTrials.gov: NCT04717479). There are currently no approved small-molecule drugs that directly modulate MFSD8 activity.

Other names

CLN7Ceroid-lipofuscinosis neuronal protein 7Major facilitator superfamily domain containing 8

Gene replacement therapy aimed at restoring functional MFSD8 protein expression in lysosomal membranes via viral vector delivery (ClinicalTrials.gov: NCT04717479).