Lysosomal enzyme trafficking factor (LYSET)

Lysosomal enzyme trafficking factor (LYSET) is a small Golgi-resident transmembrane protein critical for the mannose-6-phosphate (M6P)–mediated trafficking of hydrolases to lysosomes[1][3][5][6]. LYSET physically interacts with and anchors the GlcNAc-1-phosphotransferase (GNPTAB) complex in the Golgi membrane, which is required for tagging catabolic enzymes with the M6P signal essential for their lysosomal delivery[1][3][6]. Loss of LYSET results in instability and mislocalization of GNPTAB, failure of M6P modification, mis-trafficking of lysosomal enzymes, and accumulation of undigested substrates in enlarged lysosomes[1][3][6]. Pathogenic LYSET mutations in humans cause a syndrome analogous to mucolipidosis II (I-cell disease)[3]. LYSET is essential for cancer cell adaptation to nutrient stress, enabling lysosomal degradation of extracellular proteins for amino acid supply, and is also required by several pathogenic viruses for productive infection due to its role in lysosomal protease delivery[2][3][6]. There are no known drugs that directly target LYSET, but it is considered a potential therapeutic target in metabolic adaptation of tumors and viral pathogenesis[1][5][6].

Other names

TMEM251C14orf109GCAFGNPTAB cleavage and activity factorTransmembrane protein 251UPF0694 transmembrane protein C14orf109DMAN