Liver receptor homolog-1 (NR5A2) is a nuclear receptor originally identified in the liver and mostly known for its regulatory role in cholesterol and bile acid homeostasis. More recently, liver receptor homolog-1 has emerged as a key regulator of intestinal function, coordinating unanticipated actions, such as cell renewal and local immune function with important implications to common intestinal diseases, including colorectal cancer and inflammatory bowel disease. Unlike most of the other nuclear receptors, liver receptor homolog-1 acts as a constitutively active transcription factor to drive the transcription of its target genes. Liver receptor homolog-1 activity however is to a major extent regulated by different corepressors and posttranslational modifications, which may account for its tissue-specific functions. This review will provide an update on the molecular aspects of liver receptor homolog-1 action and focus on some emerging aspects of its function in normal and diseased gut.