Clinically, PRK2 is of great importance as a target for antiviral therapy, particularly anti-HCV, as its suppression leads to viral replication blockage in humans.( Outside of its role in viral suppression, PKN2 may play an essential role in various cellular processes, such as cellular proliferation, migration, and signaling pathways. Moreover, PKN2 is involved in autoinflammatory disorders, heart failure, and it is a target of interest in cancer. As concerns regarding the risk of malignancy and major adverse cardiovascular events (MACE) in patients treated with tofacitinib have been raised by the European Medicines Agency (EMA), it is important to consider the potential role of PKN2 inhibition.(49) However, in mice models, PKN2 activation was the cause of cardiac dysfunctions, and therefore, the clinical impact of PKN2 inhibition is contradictory to the risk of cancer and MACE in RA patients.