Pcsk9, also known as Proprotein convertase subtilisin/kexin type 9, is a proteolytic enzyme that plays a pivotal role in lipid metabolism. It indirectly regulates serum LDL cholesterol (LDL-C) by causing the destruction of LDL receptors on the surface of liver hepatocytes. This regulation is crucial for maintaining cholesterol homeostasis in the body [1,3,4,5].

Deleting the PCSK9 gene in mouse cancer cells (a form of KO mouse model) substantially attenuates or prevents their growth in mice in a manner that depends on cytotoxic T cells. It also enhances the efficacy of immune therapy targeted at the checkpoint protein PD1. Inhibiting PCSK9, either through genetic deletion or using PCSK9 antibodies, increases the expression of major histocompatibility protein class I (MHC I) proteins on the tumour cell surface, promoting robust intratumoral infiltration of cytotoxic T cells [2].

In conclusion, Pcsk9 is essential in regulating LDL-C levels through its impact on LDL receptors. The Pcsk9 KO mouse model has revealed its potential role in enhancing immune checkpoint therapy for cancer, indicating that targeting Pcsk9 could be a promising strategy in both cholesterol-related diseases and cancer treatment [2].