L-type amino acid transporter 1 (LAT1) (LAT1)

L-type amino acid transporter 1 (LAT1), encoded by the SLC7A5 gene, is a sodium-independent exchanger that facilitates the cellular uptake of large neutral amino acids such as leucine, phenylalanine, and tryptophan in exchange for intracellular amino acids (UniProt P52569). It functions as a heterodimeric complex with the chaperone protein CD98hc (SLC3A2), which is required for its stability and translocation to the plasma membrane (NCBI Gene ID: 8140). LAT1 is a critical regulator of cellular metabolism, as it provides the essential amino acids necessary for protein synthesis and the activation of the mTORC1 signaling pathway, which drives cell growth and proliferation (PubMed: 11387491). While its expression is relatively low in most normal adult tissues, it is highly expressed at the blood-brain barrier and is significantly upregulated in a wide variety of malignant tumors to support their high metabolic demands (PubMed: 28223434). This differential expression makes LAT1 an attractive therapeutic target in oncology, leading to the development of selective inhibitors like JPH203 (Nanvuranlat) designed to induce amino acid starvation in cancer cells (PubMed: 32665311). Additionally, LAT1 is frequently utilized as a portal for the delivery of amino acid-conjugated prodrugs and as a diagnostic biomarker through radiolabeled amino acid PET imaging.

Other names

SLC7A5Large neutral amino acids transporter small subunit 1CD98 light chainSystem L amino acid transporter 1MshE16Solute carrier family 7 member 5

Competitive inhibition of large neutral amino acid transport, specifically leucine, which leads to the suppression of the mTORC1 signaling pathway and subsequent inhibition of protein synthesis and cell proliferation.