SPNS lysolipid transporter 2, sphingosine-1-phosphate (SPNS2)

SPNS lysolipid transporter 2, sphingosine-1-phosphate (SPNS2) is a membrane transporter in the major facilitator superfamily (MFS), encoded by the SLC63A2 gene, primarily responsible for exporting sphingosine-1-phosphate (S1P) from cells, particularly into the lymphatic and vascular systems[1][2][6]. S1P is a bioactive lipid crucial for processes such as immune cell trafficking, vascular development, maintenance of tissue barrier functions, and auditory physiology[1][2]. SPNS2 establishes the S1P gradient that governs the migration of T-cells from lymph nodes and B-cells from bone marrow, and its dysfunction has been linked to hereditary sensorineural hearing loss and immune dysregulation[1]. SPNS2 is considered a promising therapeutic target for treatment of cancer, autoimmune diseases, inflammation, and organ-specific diseases by modulating S1P signaling. The only experimentally validated inhibitor to date is the small molecule 16d, which prevents S1P export by locking SPNS2 in an inactive conformation[2][6].

Other names

Sphingosine-1-phosphate transporter SPNS2SPNS2SLC63A2Protein spinster homolog 2solute carrier family 63 member 2DFNB115SLC62A2sphingolipid transporter 2spinster homolog 2

Small molecule inhibitors (such as 16d) prevent S1P export by stabilizing the inward-facing conformation of SPNS2, attenuating the S1P translocation cycle