Orphan Nuclear Receptor Genes (NR Superfamily) encode numerous Orphan Nuclear Receptor (NRs) transcription factors thought to be activated by as yet unknown ligands. Transducing cellular signals into gene transcription, NRs regulate development, pattern formation, cell proliferation, cell differentiation, and homeostasis in target tissues. NRs share a common organization: an (N) modulatory domain, a conserved central Cys-rich region of two C4 zinc fingers that bind to specific upstream ligand-responsive target DNA elements, and a (C) ligand-binding domain. Stabilizing hydrophobic zinc finger interactions contribute to DNA binding specificity, homodimerization, and interaction with other proteins. Ligand-bound NR conformation allows coactivator interaction with the ligand-binding domain that mediates interaction with heat shock proteins, cyclophilins, and ligand. (NCI) [ ]