Solute carrier family 38 member 2, SLC38A2, also known as sodium-coupled neutral amino acid symporter 2, system A amino acid transporter 2 (ATA2), and system N amino acid transporter 2 (SNAT2), is a cotransporting symporter of neutral amino acids and sodium ions across the cell membrane with a 1:1 stoichiometry.^1,2

The mechanism of transport of SLC38A2 is pH-sensitive, Na⁺ dependent, Li⁺-intolerant, and exhibits specificity for short-chain neutral amino acids. SLC38A2 is composed of 506 amino acids and possesses 11 transmembrane domains with an intracellular N terminus and an extracellular C-terminus, as indicated by hydropathy analysis. Competition experiments demonstrate that human SLC38A2 recognizes multiple neutral amino acids as substrates, including alanine, glycine, serine, proline, methionine, asparagine, glutamine, threonine, and leucine. Since the transport of each neutral amino acid into the cell results in the net movement of one positive charge, the process is electrogenic. SLC38A2 also modulates a leak anion current, which is mediated by the binding of Na⁺, can be inhibited to different extents by substrate transport, and is thermodynamically uncoupled from Na⁺ and substrate transport.^1,3

As demonstrated by Northern blot analyses, human tissue distribution of SLC38A2 mRNA is ubiquitous and has been identified in brain, colon, heart, kidney, liver, lung, muscle, placenta, small intestine, spleen, stomach, and testis.¹ 

SLC38A2 has been implicated in the pathophysiology of various medical conditions, such as cancer, neurological diseases, and diabetes mellitus. SLC38A2-dependent osmoadaptation has been implicated in heart failure, central pontine myelinolysis, and dry eye syndrome.

SLC38A2 is believed to participate in the transport of glutamine from astrocytes to neurons through the glutamate-glutamine cycle.²

Slc38a2 contributes to the pathology in a number of diseases such as cancer, epilepsy and diabetes mellitus.^2,3,4

Several studies have suggested that SLC38A2/SNAT2 plays a significant role in cancer by affecting the nutrient supply to cancer cells. Cancer cells have a high demand for amino acids to support their rapid growth and proliferation. SNAT2 facilitates the transport of amino acids, such as glutamine and leucine, into cancer cells. These amino acids are crucial for energy production, protein synthesis, and other metabolic processes necessary for tumor growth.⁴

Additionally, SLC38A2/SNAT2 has been linked to the mTOR (mammalian target of rapamycin) signalling pathway, a key regulator of cell growth and metabolism. Activation of mTOR signalling is commonly observed in cancer cells and contributes to their uncontrolled growth. SNAT2-mediated amino acid transport is thought to influence mTOR activity, potentially promoting cancer cell survival and proliferation.^4,5

Moreover, the expression of SLC38A2/SNAT2 has been found to be dysregulated in various cancer types. Increased expression of SNAT2 has been observed in some tumors, and this overexpression is often associated with poor prognosis and aggressive tumor behaviour. In contrast, reduced expression of SNAT2 has been reported in other cancers.^5-7

Due to its potential importance in cancer progression, SLC38A2/SNAT2 has garnered attention as a potential therapeutic target. Inhibiting SNAT2-mediated amino acid transport could be explored as a strategy to hinder cancer cell growth and sensitize tumors to existing treatments.^5-7