PIGK encodes the catalytic subunit of the glycosylphosphatidylinositol-anchor (GPI-anchor) transamidase (GPI-T) complex, which is essential for GPI-anchored protein biosynthesis 1. The protein contains a critical C206-H164-N58 triad that catalyzes the transamidation reaction, which attaches GPI anchors to target proteins by recognizing C-terminal signal peptide regions and replacing them with GPI anchors through a two-phase mechanism 1. The GPI-T complex localizes to the endoplasmic reticulum membrane where it facilitates the covalent attachment between proteins and GPI anchors embedded in the plasma membrane 2. Loss-of-function variants in PIGK cause inherited GPI deficiency disorders characterized by neurodevelopmental delay, hypotonia, cerebellar atrophy, seizures, and growth impairment 2 3. Studies using zebrafish and mouse models demonstrate that PIGK deficiency leads to extensive neuronal apoptosis, motor neuronal dysplasia, and embryonic lethality, highlighting its essential role in embryonic and neuronal development 3. Additionally, PIGK expression is regulated by genetic polymorphisms, with certain variants associated with reduced protein expression in colorectal and hepatocellular cancers 4. The protein is also subject to quality control through the SEL1L-HRD1 ERAD pathway, which targets PIGK for proteasomal degradation to regulate GPI-anchored protein biogenesis 5.