{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nStomatin‐like protein 2 (STOML2), also known as SLP2, is a member of the SPFH (stomatin, prohibitin, flotillin, HflC/K) superfamily that primarily localizes to the mitochondrial inner membrane, where it functions as a membrane organizer. By binding to the mitochondrial phospholipid cardiolipin and recruiting prohibitins, STOML2 facilitates the formation of cardiolipin‐enriched microdomains that optimize the assembly and activity of respiratory complexes and promote mitochondrial biogenesis."}, {"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 its role in organizing mitochondrial membranes, STOML2 anchors a large protease complex that includes the rhomboid protease PARL and the i‐AAA protease YME1L. This SPY complex regulates the processing of key substrates such as PINK1 and PGAM5, while also modulating stress‐activated proteases like OMA1. Through these actions, STOML2 contributes to the quality control of mitochondria and helps preserve mitochondrial dynamics during cellular stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its mitochondrial functions, STOML2 has important roles in T cell physiology. In activated T lymphocytes, STOML2 expression is upregulated and the protein is found not only within mitochondria but also associated with the plasma membrane, where it coalesces at the immunological synapse. This dual localization enables STOML2 to facilitate the assembly of T cell receptor (TCR) signalosome components and sustain robust signaling, which is essential for effective T cell activation and effector differentiation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAberrant expression of STOML2 is also linked to oncogenic processes. Overexpression has been observed in various cancers—including endometrial adenocarcinoma, breast cancer, and hepatocellular carcinoma—where it contributes to enhanced cell proliferation, increased resistance to apoptosis, and poorer clinical outcomes. These findings suggest that STOML2 not only plays a pivotal role in normal mitochondrial and immune functions but also represents a promising prognostic biomarker and potential therapeutic target in cancer."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Liudmilla Lapatsina, Janko Brand, Kate Poole, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Stomatin-domain proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Cell Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejcb.2011.01.018"}], "href": "https://doi.org/10.1016/j.ejcb.2011.01.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21501885"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21501885"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Darah A Christie, Caitlin D Lemke, Isaac M Elias, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Stomatin-like protein 2 binds cardiolipin and regulates mitochondrial biogenesis and function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.05393-11"}], "href": "https://doi.org/10.1128/MCB.05393-11"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21746876"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21746876"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Timothy Wai, Shotaro Saita, Hendrik Nolte, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The membrane scaffold SLP2 anchors a proteolytic hub in mitochondria containing PARL and the i-AAA protease YME1L."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embr.201642698"}], "href": "https://doi.org/10.15252/embr.201642698"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27737933"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27737933"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Darah A Christie, Panagiotis Mitsopoulos, Julianna Blagih, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Stomatin-like protein 2 deficiency in T cells is associated with altered mitochondrial respiration and defective CD4+ T cell responses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1103829"}], "href": "https://doi.org/10.4049/jimmunol.1103829"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23028053"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23028053"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Darah A Christie, Mark G Kirchhof, Santosh Vardhana, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitochondrial and plasma membrane pools of stomatin-like protein 2 coalesce at the immunological synapse during T cell activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0037144"}], "href": "https://doi.org/10.1371/journal.pone.0037144"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22623988"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22623988"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Mark G Kirchhof, Luan A Chau, Caitlin D Lemke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Modulation of T cell activation by stomatin-like protein 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.181.3.1927"}], "href": "https://doi.org/10.4049/jimmunol.181.3.1927"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18641330"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18641330"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Zhumei Cui, Liyong Zhang, Zhen Hua, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Stomatin-like protein 2 is overexpressed and related to cell growth in human endometrial adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2007)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17342323"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17342323"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Wenfeng Cao, Bin Zhang, Yanxue Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High-level SLP-2 expression and HER-2/neu protein expression are associated with decreased breast cancer patient survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Clin Pathol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1309/C6X54HRB580EP2NQ"}], "href": "https://doi.org/10.1309/C6X54HRB580EP2NQ"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17709317"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17709317"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yahui Zheng, Chong Huang, Lu Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "STOML2 potentiates metastasis of hepatocellular carcinoma by promoting PINK1-mediated mitophagy and regulates sensitivity to lenvatinib."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hematol Oncol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13045-020-01029-3"}], "href": "https://doi.org/10.1186/s13045-020-01029-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33446239"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33446239"}]}]}]}