A study published in the American Journal of Kidney Diseases presents a paradox: In chronic kidney disease (CKD), a significant decline in the activity of key high-density lipoprotein (HDL)-related enzymes such as paraoxonase 1 (PON1), nitric oxide (NO) synthase (NOS), and LCAT results in a reduction of HDL-C’s functional activity, subsequently transitioning it into a proinflammatory state. The gene discussed is LCAT; the disease is chronic kidney disease.