PI3Ks are a family of lipid kinases involved in the key processes of cell growth, proliferation, differentiation, motility, survival and intracellular trafficking. The PIK3R5 gene encodes a protein that functions as the regulatory subunit of the heterodimeric PI3K gamma complex. The PIK3R5 protein helps recruit the catalytic subunit of the PI3K complex to the plasma membrane via interaction with beta-gamma G protein dimers. It hence plays an essential role in the formation of the PI3K complex.
Given its crucial role in cellular processes, it is easy to see how defects in the gene can have severe pathological consequences. Mutations in the PIK3R5 gene are associated with Ataxia-Oculomotor Apraxia 3 (AOA3), a cerebellar ataxia characterized by peripheral neuropathy, areflexia, cerebellar atrophy, oculomotor apraxia and raised alpha-fetoprotein levels.