Since PCSK9 has a variety of functions outside the liver, not all of which are fully understood, the EGFA-GPA mice reported here could serve as a model to systematically explore the function of circulatory PCSK9 in the pathogenesis of diabetes, inflammation, sepsis, viral infections, and especially, obesity. The gene discussed is GYPA; the disease is obesity due to melanocortin 4 receptor deficiency.