Defective SLC17A5 causes Salla disease (SD) and ISSD

SLC17A5 encodes a lysosomal sialic acid transporter, sialin (AST, membrane glycoprotein HP59) which exports sialic acid (N-acetylneuraminic acid, Neu5Ac) derived from the degradation of glycoconjugates from lysosomes. This export is dependent on the proton electrochemical gradient across the lysosomal membrane. SLC17A5 is present in the pathological tumor vasculature of the lung, breast, colon, and ovary, but not in the normal vasculature, suggesting that the protein may be critical to pathological angiogenesis. Sialin is not expressed in a variety of normal tissues, but is significantly expressed in human fetal lung. Defects in SLC17A5 cause Salla disease (SD) and infantile sialic acid storage disorder (ISSD aka N-acetylneuraminic acid storage disease, NSD). These diseases belong to the sialic acid storage diseases (SASDs) and are autosomal recessive neurodegenerative disorders characterised by hypotonia, cerebellar ataxia and mental retardation with patients excreting large amounts of free Neu5Ac in urine. ISSD is a severe infantile form of SASD with a more severe clinical course than SD.

Summary from Reactome (R-HSA-5619035), read 2026-09-23.