Neutral amino acid transporter A (SLC1A4)

Neutral amino acid transporter A (SLC1A4, ASCT1) is a sodium-dependent membrane transporter responsible for the obligatory exchange of small neutral amino acids—primarily L-serine, D-serine, L-alanine, L-cysteine, and L-threonine—across the plasma membrane[1][2][3]. It is predominantly expressed in the brain, lung, skeletal muscle, intestine, and kidney, with crucial roles in mediating physiological amino acid homeostasis particularly in astrocytes and neurons[2][3]. SLC1A4 regulates D-serine and glycine availability, modulates NMDA receptor activity, and supports the synthesis of neurotransmitters and other biomolecules[1][3]. Pathogenic mutations in SLC1A4 cause a severe autosomal recessive neurodevelopmental disorder characterized by spastic tetraplegia, thin corpus callosum, and progressive microcephaly (SPATCCM)[2][3]. SLC1A4 is functionally distinct from glutamate transporters, does not require reverse K+ or proton transport, and functions primarily as an amino acid exchanger (antiporter) rather than a unidirectional transporter[1][2][3]. Although not currently a drug target in clinical practice, it may represent a future target for neurological and psychiatric disorders involving amino acid dysregulation[1][2][3].

Other names

Alanine/serine/cysteine/threonine transporter 1ASCT1SATTASCT-1SPATCCMSolute carrier family 1 member 4Neutral amino acid transporter A

Competitive inhibition of amino acid exchange (e.g., by OH-Pro); Modulation of substrate flux (e.g., reducing extracellular D-serine by blocking uptake/release)[3]