The nuclear receptors(NRs)are an evolutionarily related family of transcription factors,which share certain common structural characteristics and regulate the expressions of various genes by recognizing different response elements.NRs play important roles in cell differentiation,proliferation,survival and apoptosis,rendering them indispensable in many physiological activities including growth and metabolism.As a result,dysfunctions of NRs are closely related to a variety of diseases,such as diabetes,obesity,infertility,inflammation,the Alzheimer\'s disease,cardiovascular diseases,prostate and breast cancers.Meanwhile,small-molecule drugs directly targeting NRs have been widely used in the treatment of above diseases.Here we summarize recent progress in the structural biology studies of NR family proteins.Compared with the dozens of structures of isolated DNA-binding domains(DBDs)and the striking more than a thousand of structures of isolated ligand-binding domains(LBDs)accumulated in the Protein Data Bank(PDB)over thirty years,by now there are only a small number of multi-domain NR complex structures,which reveal the integration of different NR domains capable of the allosteric signal transduction,or the detailed interactions between NR and various coregulator proteins.On the other hand,the structural information about several orphan NRs is still totally unavailable,hindering the further understanding of their functions.The fast development of new technologies in structural biology will certainly help us gain more comprehensive information of NR structures,inspiring the discovery of novel NR-targeting drugs with a new binding site beyond the classic LBD pockets and/or a new mechanism of action.