L-type amino acid transporter 1 (LAT1) and L-type amino acid transporter 2 (LAT2) (LAT1/LAT2)

L-type amino acid transporter 1 (LAT1, SLC7A5) and L-type amino acid transporter 2 (LAT2, SLC7A8) are sodium-independent, heterodimeric transporters that facilitate the exchange of large neutral amino acids across the plasma membrane [1, 3]. They function as light chains that require covalent association with the heavy chain chaperone CD98 (SLC3A2) for stable membrane expression and functional activity [3, 12]. LAT1 is notably overexpressed in a wide variety of human cancers, where it serves as a critical nutrient portal for essential amino acids like leucine, which in turn activates the mTORC1 signaling pathway to drive cell growth and proliferation [6, 14]. In contrast, LAT2 is more ubiquitously expressed in normal tissues, including the kidney and the blood-brain barrier, playing a role in systemic amino acid homeostasis and the efflux phase of transport [8, 11]. Pharmacological targeting of these transporters, particularly the selective inhibition of LAT1 by small molecules like JPH203 (Nanvuranlat), has emerged as a potent strategy for cancer therapy by inducing amino acid starvation and inhibiting oncogenic signaling [6, 7]. Additionally, these transporters are exploited for the delivery of amino acid-mimetic drugs such as L-DOPA and gabapentin, and serve as targets for specialized PET imaging tracers in oncology [7, 9].

Other names

SLC7A5SLC7A8System L transportersCD98 light chainsLarge neutral amino acid transporter 1Large neutral amino acid transporter 2Solute carrier family 7 member 5Solute carrier family 7 member 8

Competitive inhibition of large neutral amino acid uptake (specifically leucine), which suppresses the mTORC1 signaling pathway and induces the general amino acid control (GAAC) pathway, leading to cell cycle arrest and apoptosis [1, 6, 14].