Glycosylphosphatidylinositol anchored proteins (GPI-APs) represent a class of 
soluble proteins attached to the external leaflet of the plasma membrane by a 
post-translation modification, the GPI anchor. The 28 genes currently involved 
in the synthesis and remodelling of the GPI anchor add to the ever-growing class 
of congenital glycosylation disorders. Recent advances in next generation 
sequencing technology have led to the discovery of Mabry disease and CHIME 
syndrome genetic aetiology. Moreover, with each described mutation known 
phenotypes expand and new ones emerge without clear genotype-phenotype 
correlation. A protein database search was made for human GPI-APs with defined 
pathology to help building-up a physio-pathological mechanism from a clinical 
perspective. GPI-APs function in vitamin-B6 and folate transport, nucleotide 
metabolism and lipid homeostasis. Defining GPI-APs role in disease bears 
significant clinical implications.