The Nuclear Receptor (NR) family of transcription factors was first discovered based on the ability of some members to bind endocrine hormones such as the steroids estrogen, progesterone and testosterone. Now that the human genome has been sequenced, we know that there are 48 different NR proteins.

It is widely believed that NRs first evolved to control lipid homeostasis, and that other more recent functions are related to this central metabolic process. Lipid homeostasis is achieved by balancing the rates of lipid uptake, storage, metabolism and excretion. NRs likely evolved to carry out these roles due to their ability to bind, and thereby monitor the levels, of major lipid metabolites. As NRs diversified, they likely gained the ability to bind and regulate new types of lipids such as the steroids, lipophilic vitamins, and the large variety of externally encountered lipophilic toxins (xenobiotics). This diversification has also enabled NRs to regulate processes that need to be coordinated with lipid metabolism, such as feeding behavior, circadian and developmental timing, sexual dimorphism and sexually dimorphic behaviors.

Diseases controlled and treatable by Nuclear Receptor-directed hormones and drugs include the vast majority of current society's most devastating and costly pandemics. These include most cancers, obesity and diabetes, anxiety and depression, inflammation and immune disorders and even aging. Current Nuclear Receptor-directed drugs garner annual revenues in the billions of dollars.