GPI-anchor transamidase

PIGK (GPI-anchor transamidase) is the catalytic subunit of the glycosylphosphatidylinositol-anchor transamidase complex, which catalyzes formation of the GPI-anchor linkage to proproteins during GPI-anchored protein biosynthesis (UniProt: Q92643). The enzyme recognizes diverse proproteins at their C-terminal signal peptide and catalyzes transamidation through a two-phase mechanism involving acyl-enzyme intermediate formation and GPI-anchor attachment. PIGK is expressed across mammalian tissues and is essential for synthesizing the large class of GPI-anchored cell-surface proteins involved in cell signaling and immunity.

Mutations in PIGK cause neurodevelopmental disorder with hypotonia and cerebellar atrophy with or without seizures (NEDHCAS, MIM 618879), an autosomal recessive condition characterized by developmental delay, intellectual disability, hypotonia, cerebellar ataxia, and epilepsy (UniProt: Q92643). This disease association underscores PIGK's critical role in neuronal development and cerebellar function.

PIGK is down-regulated in Alzheimer's disease brain tissue. In post-mortem AD brain versus age-matched controls, PIGK showed a mean log2 fold-change of −0.96 across proteomics fractions (Chaparral AD proteomics). This reduction may reflect impaired GPI-anchor biosynthesis and altered cell-surface protein presentation in AD pathogenesis.