Large neutral amino acids transporter small subunit 1 (LAT1) (LAT1)

Large neutral amino acids transporter small subunit 1 (LAT1), encoded by the SLC7A5 gene, is a sodium-independent amino acid exchanger that forms a functional heterodimer with the glycoprotein CD98hc (SLC3A2) (UniProt P50440). It is primarily responsible for the cellular uptake of essential large neutral amino acids, such as leucine, isoleucine, and phenylalanine, which are critical for protein synthesis and the activation of the mTORC1 signaling pathway (PubMed: 29113921). While its expression is limited in most normal adult tissues, LAT1 is significantly upregulated in a wide variety of human cancers to meet the high metabolic demands of proliferating tumor cells (PubMed: 31906015). This differential expression makes LAT1 an attractive therapeutic target for small molecule inhibitors like JPH203 and a strategic portal for the delivery of amino acid-mimetic chemotherapy drugs and diagnostic radiopharmaceuticals (NCBI Gene: 6541). Beyond oncology, LAT1 plays a vital role in transporting drugs across the blood-brain barrier, influencing the pharmacokinetics of central nervous system acting agents like Levodopa (PubMed: 30241014).

Other names

SLC7A5L-type amino acid transporter 1CD98 light chain4F2 light chain4F2LCSolute carrier family 7 member 5

LAT1 acts as a sodium-independent exchanger that imports essential amino acids like leucine into cells in exchange for intracellular glutamine (PubMed: 29113921). Drugs targeting LAT1 typically act as competitive inhibitors to starve cancer cells of nutrients or utilize the transporter as a vehicle for prodrug delivery into the cytoplasm or across the blood-brain barrier (PubMed: 31906015).