PCSK9 is a key regulator of plasma cholesterol homeostasis that promotes the degradation of low-density lipoprotein receptors (LDLR) and related receptors through non-proteolytic mechanisms 1. PCSK9 binds to LDLR, VLDLR, LRP1, and LRP8, directing them to lysosomes for degradation and preventing their recycling from endosomes to the cell surface 1. This reduces hepatocyte LDLR expression, thereby increasing serum LDL cholesterol levels. Gain-of-function PCSK9 mutations cause familial hypercholesterolemia, while loss-of-function mutations are cardioprotective 2. Beyond cholesterol metabolism, PCSK9 regulates MHC class I protein recycling on tumor cell surfaces; inhibiting PCSK9 increases MHC I expression and enhances immune checkpoint therapy efficacy in cancer models 3. Clinically, PCSK9 inhibitors—including monoclonal antibodies (evolocumab, alirocumab, tafolecimab) and siRNA (inclisiran)—reduce LDL cholesterol by 40-70% and lower cardiovascular events 4. These inhibitors represent major advances for patients intolerant of statins or requiring additional LDL-C reduction 2. Emerging evidence suggests PCSK9 may serve as a prognostic indicator and therapeutic target in cancer 5.