The SARS-CoV-2 papain-like protease (PLpro) plays an essential role in processing viral proteins needed for replication. In addition, the enzyme can cut and inactivate some human proteins important for an immune response. Now, researchers reporting in ACS Infectious Diseases have found other targets of PLpro in the human proteome, including proteins involved in cardiovascular function, blood clotting and inflammation, suggesting a link between the inactivation of these proteins and COVID-19 symptoms.