MORF4L1 (mortality factor 4-like 1) is a multifunctional chr15 remodeling protein that participates in diverse nuclear processes through association with distinct protein complexes. MORF4L1 is a core component of the NuA4 histone acetyltransferase complex, which acetylates histones H4 and H2A to promote transcriptional activation 1. It also associates with the Sin3B histone deacetylase complex, ASH1L histone methyltransferase complex, and PALB2-BRCA2 DNA repair complexes 1. In DNA repair, MORF4L1 enhances homologous recombination by acetylating PALB2 at lysine 628, preventing its degradation, and facilitating H3K4 acetylation to recruit repair factors 2. Beyond nuclear functions, MORF4L1 localizes to mitochondria where it deacetylates TUFM (mitochondrial translation elongation factor), leading to TUFM degradation by the ClpXP protease system and subsequent mitochondrial dysfunction 34. MORF4L1 is upregulated in various cancers including hepatocellular carcinoma and contributes to radiotherapy resistance 25. In liver disease, elevated MORF4L1 promotes NASH progression through mitochondrial dysfunction and inflammasome activation 3. The protein is regulated by deubiquitinase USP53, which stabilizes MORF4L1 and suppresses colorectal cancer growth 6.