Cardiovascular disease remains a leading cause of death worldwide, with low-density lipoproteins and other atherogenic lipoproteins, such as lipoprotein remnants, playing a key role in the development of atherosclerosis. Beyond LDL cholesterol, the identification of biological, environmental, and genetic markers associated with remnant metabolism has improved cardiovascular risk prediction and informed treatment strategies. This Reprint examines rare and severe lipid disorders, including homozygous familial hypercholesterolemia, refractory hypercholesterolemia, and severe hypertriglyceridemia, which continue to present major therapeutic challenges despite maximally tolerated lipid-lowering therapies. It also highlights the rapid development of novel inhibitors such as PCSK9, ANGPTL3, and APOC3, as well as emerging therapies derived from new mechanistic pathways. In addition, the link between metabolic conditions such as non-alcoholic steatohepatitis and cardiovascular events is explored. Collectively, the articles in this Reprint provide a comprehensive and up-to-date overview of current advances, ongoing challenges, and future perspectives in lipid modification and cardiovascular risk management.

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