A study published in Nature Communications by the Department of Molecular and Integrative Physiology’s Dr. Jongsook Kim Kemper and colleagues shows the role of RanBP2-mediated SUMO modification of an orphan nuclear receptor Small Heterodimer Partner (SHP) in maintaining bile acid (BA) homeostasis. Bile Acids are signalling molecules that profoundly affect metabolism but they have detergent-like toxicity and their levels in the liver must be tightly regulated. SHP takes part in this regulation, but how it senses the BA signal for regulation through feedback transnational responses is still unclear. The study uncovered an unexpected function of a nucleoporin RANBP2 in maintaining BA homeostasis through SUMOylation of SHP. Upon BA signalling, RanBP2 SUMOylates SHP at K68, which is required for nuclear transport and the gene repression function of SHP in feedback inhibition of BA biosynthesis.