Mortality factor 4-like 1 (MORF4L1) is a highly ubiquitinated protein, initially discovered for its role in reversing cellular immortalization. It functions as a component of multi-subunit complexes, including the NuA4 (nucleosome acetyltransferase of H4) histone acetyltransferase, SIN3B histone deacetylase complexes, and histone methyltransferase. It thereby directly influences histone acetylation, methylation, and gene expression. MORF4L1 has emerged as a key player in several biological processes, such as chromatin remodeling, DNA damage response, and cellular senescence. Recent research findings highlight its expanded role in lipid metabolism and metabolic diseases. Genome-wide association studies reveal single-nucleotide polymorphisms near the MORF4L1 locus correlating with lipid traits, type 2 diabetes, and coronary artery disease. This review provides a comprehensive overview of MORF4L1's regulation and its multifaceted roles, implicating its emerging importance in vascular homeostasis and cardiometabolic disease. We propose that MORF4L1's intricate mechanisms demand a deeper understanding. As a regulatory protein at the interface of chromatin biology, cellular senescence, and lipid metabolism, MORF4L1 holds promise as a potential therapeutic target for ameliorating vascular and metabolic dysfunction in cardiometabolic diseases.
Tanni et al. (Sun,) studied this question.