SPNS1 functions as a critical lysosomal transporter mediating the rate-limiting, proton-dependent efflux of lysophospholipids from lysosomes to the cytosol 12. The protein selectively transports zwitterionic lysophospholipids including lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), and lysoplasmalogen, facilitating phospholipid salvage through subsequent reacylation by cytosolic acyltransferases 12. Mechanistically, SPNS1 utilizes a five-residue network for proton sensing and specific transmembrane domains for substrate recognition, with LPC binding within a luminal-open cavity 3. Disease relevance is significant, as SPNS1 deficiency causes lysosomal storage disease characterized by accumulation of sphingosines and lysoglycerophospholipids, leading to embryonic lethality, liver dysfunction, and altered PI3K/AKT signaling in mouse models 4. Human patients with biallelic SPNS1 variants present with multiorgan disease including progressive liver injury, striated muscle damage, and neurological impairment 54. Clinically, SPNS1 dysfunction affects mTOR-regulated lipid homeostasis, reduces triglyceride synthesis, and impairs cellular energy storage under nutrient limitation 5. Additionally, SPNS1 serves as an essential factor for enterovirus infections by transporting viral pocket factors 6.