Solute carrier family 17 member 5 (SLC17A5)

Solute carrier family 17 member 5 (SLC17A5), commonly known as Sialin, is a lysosomal membrane protein responsible for the export of free sialic acid from lysosomes through a proton-coupled mechanism, thereby maintaining sialic acid homeostasis in cells[1][2][3]. Sialin belongs to the SLC17 transporter family, distinct in its ability to transport sialic acid, nitrate, and certain acidic neurotransmitters like glutamate and N-acetylaspartylglutamate (NAAG)[2][3][4]. It can switch between different substrate transport modes depending on cellular localization—lysosomal sialic acid efflux, plasma membrane nitrate uptake, or vesicular neurotransmitter accumulation. Genetic mutations disrupting SLC17A5 lead to severe lysosomal storage diseases such as Salla disease and infantile sialic acid storage disorder, both characterized by excessive accumulation of sialic acid and progressive neurodegeneration[1][2][3][4]. Sialin’s physiological roles extend to neural transmission, glycan biosynthesis, and nitrate clearance in salivary glands. While no approved drugs directly target SLC17A5 clinically, inhibitors and substrate analogs have been used experimentally, providing molecular insights into transporter function and disease mechanisms[3].

Other names

SialinASTVEATSDISSDNSDSIALINSLDH(+)/nitrate cotransporterH(+)/sialic acid cotransporterMembrane glycoprotein HP59Vesicular excitatory amino acid transporterAcidic sugar transporterInfantile sialic acid storage disorderSalla diseaseSIASDSodium/sialic acid cotransporter

Competitive inhibition of sialic acid transport (by molecules binding transporter substrate sites); Modulation of substrate binding (e.g., NAAG and sialic acid occupy overlapping binding sites within the transporter); Interference with transporter conformational changes (as demonstrated by pathogenic mutations); Experimental inhibition of vesicular neurotransmitter accumulation