Solute carrier family 46 member 2 (SLC46A2)

Solute carrier family 46 member 2 (SLC46A2) is a membrane transporter belonging to the SLC46 family, predominantly expressed in cortical thymic epithelial cells and select other epithelial tissues such as skin, lung, spleen, lymph nodes, bone marrow, and fetal liver. SLC46A2 mediates the transmembrane import of cyclic dinucleotides, notably cyclic-GMP-AMP (cGAMP), and DAP-type muropeptides from bacteria, integrating microbial signals into cytosolic pattern recognition receptor pathways (NOD1, NOD2, STING), thereby activating innate immune responses and cytokine release. It has been implicated in suppressing tumor progression in lung and cervical tissues, with reduced expression observed in several lung cancers and associations with cervical cancer susceptibility. In monocyte-derived macrophages, SLC46A2 is the dominant importer of extracellular cGAMP, whereas its inhibition by sulfasalazine impairs this immune activation pathway. Additionally, it is a marker for thymic epithelial stem cell subsets and may play a role in establishing immune tolerance.

Other names

TSCOTLy110Thymic stromal cotransporter homologthymic stromal co-transporterthymic stromal cotransporterSLC46A2

Inhibition of SLC46A2 by specific drugs (e.g., SSZ) can reduce extracellular cGAMP import and downstream innate immune activation in macrophages