2025/09/02
paper · doi:10.17912/micropub.biology.001733
<p>Lysosomal free sialic acid storage disorder (FSASD) is an ultra-rare neurodegenerative condition caused by mutations in <i>SLC17A5</i>, which encodes the lysosomal sialic acid exporter, sialin. Deficiency of sialin leads to lysosomal accumulation of unconjugated (“free”) sialic acid. This study investigated the ability of N-acetylmannosamine (ManNAc), a precursor of sialic acid, to rescue glycosphingolipid (GSL) sialylation in a SLC17A5-deficient HEK-293T model system. Our findings reveal that while ManNAc supplementation may enhance sialic acid biosynthesis, it does not fully restore ganglioside sialylation to wild-type levels, highlighting the essential role of lysosomal sialic acid recycling in maintaining GSL sialylation homeostasis.</p>