This special lipid-themed issue of JACC emphasizes the importance of innovative research in lipid disorders to reduce cardiovascular risk, highlighting studies that extend our understanding of lipid biology and evaluate new treatments. Key reviews and original investigations explore novel lipid-modifying therapies, such as RNA interference and antibody therapies, demonstrating their potential in managing complex lipid disorders. The issue also includes editorials and case studies that provide critical context and underscore the need for personalized and mechanism-driven approaches in lipid management.