Signal transduction via nuclear hormone receptors is important for cell growth and differentiation, development, and homeostasis. Nuclear hormone receptors are ligand-activated transcription factors that modulate target gene expression. These ligand/receptor complexes also interact with transcriptional coactivators which enhance ligand-dependent transcription. Various classes of coactivators have been identified, including SRC-1 and its related proteins, such as TIF-2/GRIP-1, RIP140, AIB-1, and TIF-1α and -1β. AIB-1 (Amplified In Breast cancer-1) is also known as pCIP, RAC3, and TRAM-1. It interacts with estrogen receptor (ER) and is overexpressed in breast cancer biopsies and several breast and ovarian cancer cell lines. Similar to SRC-1 and TIF2, AIB-1 contains a basic helix-loop-helix (bHLH) domain followed by a PAS (Per/Arnt/Sim) region, serine and threonine rich regions, and a charged cluster. In addition, AIB-1 contains three copies of the conserved LXXLL motif which is critical to its interaction with the nuclear receptor. Thus, AIB-1 is a coactivator of nuclear receptors that may participate in the development of steroid-dependent cancers.