Furthermore, RNF216 is also a negative regulator of TLR8 signaling by targeting TLR8 for K48-linked ubiquitination and degradation after stimulation by RNA ligands.191 The RNF216 expression significantly decreases in Critically Ill Subjects at Risk for or with acute respiratory distress syndrome (ARDS), implicating that the downregulation of RNF216 may contribute to potentiate excessive inflammation in subjects with or at risk for ARDS. Here, TLR8 is linked to acute respiratory distress syndrome.