In article number 2002680, Jun Cui and co-workers identify a new histone modifier-USP38, that modulates histone ubiquitination and methylation to resolve inflammatory response. USP38 acts as a “Safety Machine” which shuts down the inflammation by de-ubiquitinating histone H2B and stabilizes KDM5B to de-methylate H3K4, which blocks the transcription of pro-inflammatory genes. The USP38-KDM5B complex might be a potential clinical target for therapy against inflammatory diseases.