PGAP1 (post-GPI attachment to proteins inositol deacylase 1) is an endoplasmic reticulum-localized serine hydrolase that catalyzes removal of the acyl chain from the 2-OH position of the inositol ring in glycosylphosphatidylinositol-anchored proteins (GPI-APs) 1. This deacylation initiates the post-attachment remodeling phase essential for GPI-AP biogenesis and facilitates ER-to-Golgi transport of properly modified GPI-APs 21. Structural studies reveal PGAP1's distinctive guitar-shaped substrate-binding cavity and drawing compass-like conformational movement during catalysis, with glycan-mediated interactions conferring substrate specificity 1. Clinically, PGAP1 deficiency causes spastic paraplegia-67, an autosomal recessive neurodevelopmental disorder characterized by psychomotor retardation, dysmorphic features, spasticity, brain atrophy, and delayed myelination 34. Affected individuals also present with cerebral visual impairment, intellectual disability, microcephaly, and increased susceptibility to respiratory complications including recurrent apneas 35. Loss-of-function PGAP1 variants prevent GPI-AP remodeling, demonstrable through reduced resistance to phosphatidylinositol-specific phospholipase C treatment in patient-derived lymphoblastoid cells 5. Beyond neurological manifestations, PGAP1 appears involved in immune regulation and fibrotic disease pathways 67, suggesting broader disease relevance.