GLTPD1 Human

The GLTPD1 gene is located on chromosome 1p36.33 and consists of three exons . The protein encoded by this gene contains 214 amino acids and has a molecular mass of approximately 26.8 kDa . The recombinant human GLTPD1 is produced in E. coli and is a single, non-glycosylated polypeptide chain .

GLTPD1 mediates the transfer of ceramide-1-phosphate, a sphingolipid, between intracellular membranes . This transfer is essential for maintaining the normal structure of the Golgi stacks and other cellular functions . The protein has a unique two-layered alpha-helical topology with a positively charged surface cavity for anchoring the lipid phosphate head group and a deep interior hydrophobic cavity to accommodate sphingosine and acyl chains .

GLTPD1 is expressed in various human tissues, with the highest expression observed in the placenta, kidney, pancreas, and testis . Immunohistochemical analysis has revealed that GLTPD1 is localized in the cytosol and is associated with the trans-Golgi network (TGN), endosomes, nucleus, and plasma membrane .

The crystal structure of purified human GLTPD1 in complex with 16:0-C1P has been determined to a resolution of 1.9 angstroms . The protein exhibits two lipid-binding conformations: the ‘sphingosine-in’ mode, where both ceramide chains occupy the hydrophobic pocket, and the ‘sphingosine-out’ mode, where only the acyl chain occupies the pocket . Mutation analysis has identified lysine 60 and arginine 106 as critical for head group recognition .

Research has shown that knockdown of GLTPD1 using small interfering RNA (siRNA) elevates cellular content of certain C1P species, decreases cellular content of sphingosines, sphingomyelins, and ceramides, and induces fragmentation of Golgi cisternal stacks . Accumulation of C1P in the TGN following siRNA against GLTPD1 increases proinflammatory arachidonic acid and eicosanoid generation . These findings suggest that GLTPD1 plays a significant role in regulating lipid metabolism and inflammatory responses.