MFSD8 encodes a lysosomal membrane protein that functions as an outward-rectifying chloride channel involved in endolysosomal homeostasis. The protein localizes to endocytic compartments including acidic intracellular vesicles and late endosomes 1. MFSD8 influences protein secretion, particularly affecting the secretion of cathepsin D and CLN5 1. Loss of MFSD8 function leads to autophagy failure, resulting in accumulation of structurally and bioenergetically impaired mitochondria in neurons 2. This dysfunction causes elevated mitochondrial reactive oxygen species that aberrantly activates the glycolytic enzyme PFKFB3, contributing to disease pathogenesis 2. MFSD8 mutations cause CLN7 neuronal ceroid lipofuscinosis, a fatal neurodegenerative lysosomal storage disease 3. The clinical spectrum ranges from severe infantile forms to isolated adult-onset macular dystrophy without systemic symptoms 4. Gene therapy approaches using AAV9/MFSD8 have shown promise in preclinical models, demonstrating dose- and age-dependent therapeutic effects including normalized behaviors and doubled median lifespan 5. MFSD8 has also been implicated as a risk factor in amyotrophic lateral sclerosis and frontotemporal dementia 6.