When the human genome project was completed in 2003, it revealed that we have roughly 22,000 different genes (see DNA 101). But not every gene is active in every cell at all  times. A skin cell doesn’t need to express the same genes as a liver cell. And a liver cell doesn’t always need to express the genes necessary to process alcohol, unless triggered to do so. To conserve resources and function properly, cells have many ways to control which genes are on, which are off and when to switch that up.

One way to regulate gene expression is with nuclear receptors – proteins that directly bind to DNA to turn genes on or off in response to outside signals. There are 48 known nuclear receptor family members. For some, it’s well known what turns them on or off and what genes they activate or inactivate in response. The estrogen receptor is a nuclear receptor that receives estrogen, the female hormone, and switches on genes that drive female characteristics. For other nuclear receptors, the orphan receptors, all we really know is that they resemble other family members. Their function and their binding partners remain a mystery.

Nuclear receptors make good drug targets because they have open pockets just waiting to hold a signaling molecule. Drug compounds can also be made to fit these pockets, switching the nuclear receptor on or off to alter gene expression. The breast cancer drug tamoxifen, for example, targets the estrogen receptor.