Defects in this gene are the cause of nonspherocytic hemolytic anemia, and a severe enzyme deficiency can be associated with hydrops fetalis, immediate neonatal death and neurological impairment.

[provided by RefSeq, Jan 2014][5] Functional GPI is a 64-kDa dimer composed of two identical monomers.

[9] It is hypothesized that serine phosphorylation of this protein induces a conformational change to its secretory form.

The ring is opened in a "push-pull" mechanism by His388, which protonates the C5 oxygen, and Lys518, which deprotonates the C1 hydroxyl group.

[9] Outside the cell, it functions as a neurotrophic factor for spinal and sensory neurons, called neuroleukin.

[13] The same protein is also secreted by cancer cells, where it is called autocrine motility factor[14] and stimulates metastasis.

[18] Cloning experiments also revealed that GPI is identical to the protein known as autocrine motility factor (AMF).

[20] AMF is thought to play a key role in cancer metastasis by activating the MAPK/ERK or PI3K/AKT pathways.

Though not closely related to eukaryotic GPIs, the bifunctional enzyme is similar enough that the sequence includes the cluster of threonines and serines that forms the sugar phosphate-binding site in conventional GPI.

[27] Elevated serum GPI levels have been used as a prognostic biomarker for colorectal, breast, lung, kidney, gastrointestinal, and other cancers.

As a result, GPI activity likely confers resistance in breast cancer cells against HER2-based therapies using Herceptin/Trastuzumab, and should be considered as an additional target when treating patients.

[23] Human GPI is capable of inducing arthritis in mice with varied genetic backgrounds via intradermal injection.