Structure and function of the atypical orphan nuclear receptor small heterodimer partner

The small heterodimer partner (SHP; NROB2) is a member of the nuclear receptor superfamily and is classified as an "orphan" subgroup, as its ligand has not yet been identified. SHP lacks the classical DNA-binding domain found in most nuclear receptors and functions as a transcriptional coregulator by directly interacting with nuclear receptors and other transcription factors. SHP regulates the transcription of a variety of target genes and controls a variety of physiological functions. For the past 10 years, great progress has been made in our understanding of the mechanism of action of SHP and the regulation of SHP gene expression. Many of the results imply that SHP has a variety of roles in the regulation of metabolic homeostasis. In this review, we discuss the current state of understanding of the structure, expression, and function of the orphan nuclear receptor, SHP.