GPI-anchor transamidase component PIGS

PIGS (GPI-anchor transamidase component) is a catalytic component of the glycosylphosphatidylinositol-anchor transamidase (GPI-T) complex (UniProt: Q96S52). It catalyzes the formation of the covalent linkage between proteins and their GPI anchors, a critical step in biosynthesis of GPI-anchored proteins that are tethered to cell membranes via glycolipid modifications.

The protein is ubiquitously expressed across tissues involved in protein synthesis and membrane trafficking. Mutations in PIGS cause glycosylphosphatidylinositol biosynthesis defect 18 (GPIBD18), a severe autosomal recessive neurodevelopmental disorder presenting with developmental delay, seizures, hypotonia, and ataxia (UniProt: Q96S52). GPI-anchor deficiency leads to impaired anchoring of protein ligands and signaling molecules critical for neuronal function.

In Alzheimer's Disease, PIGS is upregulated in post-mortem AD brain relative to age-matched controls (Chaparral AD proteomics), with a mean log₂FC of 0.35 across one subcellular fraction. This modest elevation suggests potential dysregulation of GPI-anchor biosynthesis in AD pathogenesis, though the functional consequence requires further investigation.