biostudies-literatureMassa Lopez DDeutsche ForschungsgemeinschaftEuropean Commissione50025https://www.ebi.ac.uk/biostudies/studies/S-EPMC6819133biostudies-literatureUnknown8Lysosomes are major sites for intracellular, acidic hydrolase-mediated proteolysis and cellular degradation. The export of low-molecular-weight catabolic end-products is facilitated by polytopic transmembrane proteins mediating secondary active or passive transport. A number of these lysosomal transporters, however, remain enigmatic. We present a detailed analysis of MFSD1, a hitherto uncharacterized lysosomal family member of the major facilitator superfamily. MFSD1 is not N-glycosylated. It contains a dileucine-based sorting motif needed for its transport to lysosomes. <i>Mfsd1</i> knockout mice develop splenomegaly and severe liver disease. Proteomics of isolated lysosomes from <i>Mfsd1</i> knockout mice revealed GLMP as a critical accessory subunit for MFSD1. MFSD1 and GLMP physically eLifeThe lysosomal transporter MFSD1 is essential for liver homeostasis and critically depends on its accessory subunit GLMP.PMC6819133DA 1785-1607446 EuroclastMassa Lopez DLinhorst AHermanns-Borgmeyer IThelen MStahl FThiel CEskild WDamme MSylvester MLullmann-Rauch RSaftig PfalseThe lysosomal transporter MFSD1 is essential for liver homeostasis and critically depends on its accessory subunit GLMP.Lysosomes are major sites for intracellular, acidic hydrolase-mediated proteolysis and cellular degradation. The export of low-molecular-weight catabolic end-products is facilitated by polytopic transmembrane proteins mediating secondary active or passive transport. A number of these lysosomal transporters, however, remain enigmatic. We present a detailed analysis of MFSD1, a hitherto uncharacterized lysosomal family member of the major facilitator superfamily. MFSD1 is not N-glycosylated. It contains a dileucine-based sorting motif needed for its transport to lysosomes. <i>Mfsd1</i> knockout mice develop splenomegaly and severe liver disease. Proteomics of isolated lysosomes from <i>Mfsd1</i> knockout mice revealed GLMP as a critical accessory subunit for MFSD1. MFSD1 and GLMP physically 2019-01-01T00:00:00Z2019 Oct2026-04-14T09:20:45.863Z2019-11-07T08:08:22ZS-EPMC68191333166143210.7554/eLife.50025