RWDD3 (RSUME), a small RWD-containing protein, has a central role in sumoylation by enhancing SUMO conjugation in the regulatory network of immune-inflammatory signals. RWDD3 increases IκBeta sumoylation and stability. In addition, RWDD3 inhibits TNF-α-induced kappaB-LUC (Luciferase) reporter activity, showing the functional consequence of IκBeta increased stability. RSUME-enhanced sumoylation of IκBeta leads to the inhibition of NF-κBeta activity on two well-known inflammatory genes, IL-8 and cyclooxygenase-2 (Cox-2) and therefore may also favor anti-inflammatory pathways. Expression of RWDD3 was induced under hypoxic conditions and it has a potential role during vascularization. Both BMP-4 and RWDD3 may be interesting targets for inhibiting steps involved in pituitary tumorigenesis.