Post-GPI attachment to proteins inositol deacylase 1 (PGAP1)

Post-GPI attachment to proteins inositol deacylase 1 (PGAP1) is a transmembrane enzyme located in the endoplasmic reticulum that catalyzes the removal of an acyl chain from the inositol ring of newly synthesized glycosylphosphatidylinositol (GPI) anchors after their attachment to proteins[1][5][3]. This inositol deacylation is the initial step of post-attachment lipid remodeling, which is essential for effective quality control, sorting, and secretion of GPI-anchored proteins from the ER to the cell surface[1][5][2][3]. PGAP1 has a ten-transmembrane architecture, with functional lipase and jelly-roll domains[1][4]. Deficiencies or mutations in PGAP1 cause abnormal GPI anchor structures, notably affecting neurological development and leading to autosomal recessive spastic paraplegia type 67 (SPG67), cognitive defects, and neurodevelopmental disorders[2][5][1]. In laboratory assays, loss of PGAP1 activity results in resistance of GPI-anchored proteins to cleavage by phosphatidylinositol-specific phospholipase C (PI-PLC)[2]. PGAP1 orthologs exist in yeast (Bst1), plants, and mammals[1][3]. No drugs currently target PGAP1, but its essential cellular role identifies it as a possible therapeutic target for disorders of GPI-anchor metabolism.

Other names

GPI inositol-deacylasePGAP1Post-GPI attachment to proteins factor 1hPGAP1Bst1SPG67FLJ12377UNQ3024/PRO9822ISPD3024MRT42NEDDSBA