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

Large neutral amino acids transporter 1 (LAT1), encoded by the SLC7A5 gene, is a sodium-independent transporter that mediates the uptake of essential large neutral amino acids such as leucine, isoleucine, and phenylalanine into cells (UniProt P48023). It functions as a disulfide-linked heterodimer with the glycoprotein CD98hc (SLC3A2) to facilitate amino acid exchange, which is critical for maintaining intracellular nutrient levels and activating the mTORC1 signaling pathway (PMID: 29114170). LAT1 is highly expressed in the blood-brain barrier and is significantly upregulated in various human cancers to support the high metabolic demands of rapidly proliferating cells (PMID: 31515465). Because of its overexpression in tumors and its role in nutrient signaling, LAT1 has emerged as a promising therapeutic target for oncology and a vehicle for drug delivery across the blood-brain barrier (PMID: 30115744). Several small molecule inhibitors, such as JPH203, are being investigated for their ability to starve cancer cells of essential nutrients, while drugs like melphalan and levodopa utilize LAT1 for cellular entry (PubChem). Monitoring LAT1 expression via immunohistochemistry or PET imaging with radiolabeled amino acids serves as a valuable biomarker for patient selection and treatment response (PMID: 28213373).

Other names

SLC7A5Solute carrier family 7 member 5L-type amino acid transporter 1CD98 light chain4F2 light chainMDU1

Large neutral amino acids transporter 1 (LAT1) operates as a sodium-independent, high-affinity amino acid exchanger. It transports essential neutral amino acids (such as leucine, phenylalanine, and tyrosine) into the cell in exchange for the efflux of intracellular substrates, primarily glutamine (PMID: 29114170). Drugs targeting LAT1 typically function as competitive inhibitors to block nutrient uptake and inhibit mTOR signaling in cancer cells, or they act as substrates that utilize the transporter's high expression at the blood-brain barrier or in tumors to achieve intracellular delivery (PMID: 31515465, PubChem).