{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMORC2, a member of the microrchidia family of CW‐type zinc finger proteins, has emerged as a multifaceted regulator operating in both the nucleus and the cytosol. In lipogenic breast cancer cells and differentiating adipocytes, cytosolic MORC2 interacts with enzymes like ATP‐citrate lyase (ACLY) to enhance the production of acetyl‐CoA, thereby promoting lipogenesis, adipogenic differentiation, and overall lipid homeostasis. This novel metabolic function complements its well‐established nuclear roles in transcription modulation and DNA repair."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to these metabolic activities, MORC2 is critical in maintaining genomic stability through the epigenetic silencing of retroelements in mouse embryonic stem cells. Acting via the SETDB1/TRIM28 pathway and partnering with chromatin‐remodeling complexes, MORC2 (often noted as MORC2A) aids in restricting the expression of endogenous retroviruses and proviruses, thereby preventing aberrant transcription and ensuring proper epigenetic regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMutations in MORC2 have also been implicated in a spectrum of neuropathies, ranging from peripheral (Charcot‐Marie‐Tooth disease type 2Z) to central nervous system dysfunctions associated with DIGFAN syndrome. In relevant mouse models, specific MORC2 mutations lead to the accumulation of DNA damage, impair protein synthesis, and trigger hydroxyl radical–mediated apoptotic pathways in neuronal cells. Importantly, these pathogenic insights have enabled the development of gene therapy approaches—using, for example, adeno‐associated viruses to restore normal MORC2 function and ameliorate both neuropathy and muscular dysfunction—demonstrating translational potential for treating these incurable conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Beatriz Sánchez-Solana, Da-Qiang Li, Rakesh Kumar "}, {"type": "b", "children": [{"type": "t", "text": "Cytosolic functions of MORC2 in lipogenesis and adipogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2013.11.012"}], "href": "https://doi.org/10.1016/j.bbamcr.2013.11.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24286864"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24286864"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kei Fukuda, Akihiko Okuda, Kosuke Yusa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A CRISPR knockout screen identifies SETDB1-target retroelement silencing factors in embryonic stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genome Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gr.227280.117"}], "href": "https://doi.org/10.1101/gr.227280.117"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29728365"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29728365"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Geon Seong Lee, Geon Kwak, Ji Hyun Bae, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Morc2a p.S87L mutant mice develop peripheral and central neuropathies associated with neuronal DNA damage and apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dis Model Mech (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dmm.049123"}], "href": "https://doi.org/10.1242/dmm.049123"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34695197"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34695197"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Hye Yoon Chung, Geon Seong Lee, Soo Hyun Nam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Morc2a variants cause hydroxyl radical-mediated neuropathy and are rescued by restoring GHKL ATPase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/brain/awae017"}], "href": "https://doi.org/10.1093/brain/awae017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38227798"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38227798"}]}]}]}