Insulin receptor substrates (IRS) are responsible for several insulin related activities, such as glucose homeostasis, cell growth, cell transformation, apoptosis and insulin signal transduction. Serine/threonine phosphorylation of IRS1 has been demonstrated to be a negative regulator of insulin signaling and is responsible for its degradation, although IRS1 degradation pathways are not well understood. IRS1 has also been shown to be constitutively activated in cancers such as breast cancer, Wilm's tumors, and adrenal cortical carcinomas, thus making IRS1 phosphorylation and subsequent degradation an attractive therapeutic target. To date there have been four subtypes identified: IRS1, 2, 3 and 4, with IRS1 being widely expressed.