Spinster homolog 1 (SPNS1)

Spinster homolog 1 (SPNS1) is a lysosomal membrane transporter belonging to the solute carrier family 63 (SLC63) and the major facilitator superfamily (MFS) that mediates the efflux of lysophospholipids—especially lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE)—from the lysosomal lumen to the cytosol[1][2][3][4]. This transport is essential for recycling lysolipids into phosphatidylcholine for membrane synthesis and cellular homeostasis, notably via the Lands cycle. SPNS1 activity is driven by a proton gradient and involves key residues required for substrate binding and proton sensing, critical for its transporter mechanism[1][2]. Loss‐of‐function mutations can cause lysosomal lipid accumulation, autophagic defects, and have been associated with neurodevelopmental disorders and pathologies resembling lysosomal storage diseases in animal models and humans[1][4]. SPNS1 displays selectivity for zwitterionic lysophospholipids (LPC, LPE), but does not transport anionic lysophospholipids or sphingolipids such as sphingosine-1-phosphate[3]. As of 2024, SPNS1 is not directly targeted by approved drugs, but its role in cellular metabolism suggests potential as a future therapeutic target in diseases with autophagic or lipid storage components.

Other names

Protein spinster homolog 1SPNS1SPIN1PP20300HSpin1nrsSPINLLATSLC63A1SLC62A1solute carrier family 63 member 1sphingolipid transporter 1 (putative)spinster-like protein 1