Morf4l1, also known as MRG15, is a member of a subgroup of histone acetyltransferases and belongs to the mortality factor on chromosome 4 (MORF4) class of proteins. It is a highly conserved protein in eukaryotes containing a chromodomain recognizing histone H3 lysine 36 methylation (H3K36me3) in chromatin. Morf4l1 is involved in multiple processes such as chromatin modifications, gene regulation, alternative mRNA splicing, and DNA repair, and plays a crucial role in physiological functions like lipid metabolism [1,3].

In nasopharyngeal carcinoma, ectopic expression of Morf4l1 inhibits cell proliferation, colony formation, migration and invasion by increasing p21 and E-cadherin levels, suggesting its role as a tumor suppressor [1].

In non-alcoholic steatohepatitis (NASH), MRG15 (Morf4l1) level is increased. It associates with the outer mitochondrial membrane, interacts with and deacetylates TUFM, leading to TUFM degradation, impaired mitophagy, increased oxidative stress and NLRP3 inflammasome pathway activation, thus aggravating NASH progression [2].

In hyperlipidemic acute pancreatitis, MRG15 is upregulated, inhibits mitophagy by degrading TUFM, promotes cell apoptosis and worsens the disease progression [4].

In sepsis-related liver injury, increased MRG15 in hepatocytes disturbs hepatic lipid metabolism, promotes PCSK9 synthesis and secretion, induces macrophage M1 polarization and exacerbates liver injury [5].

In conclusion, Morf4l1 is involved in diverse biological functions and is implicated in various disease conditions including cancer, NASH, hyperlipidemic acute pancreatitis and sepsis-related liver injury. Gene knockout or knockdown models in these contexts have been instrumental in revealing its role in disease-related biological processes, providing potential therapeutic targets for these diseases.