{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CALHM5 is a member of the calcium homeostasis modulator family, a group of voltage‐ and extracellular Ca²⁺–regulated ion channels that facilitate ATP and ion flux across the plasma membrane. Although CALHM1 is the best‐characterized family member—with demonstrated roles in mediating nonsynaptic neurotransmitter (ATP) release in taste bud cells and in regulating neuronal excitability in the brain (see"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "—emerging transcriptomic analyses suggest that other CALHM family members, including CALHM5, may also be functionally significant. In a pan‐cancer study examining epithelial–mesenchymal transition (EMT), CALHM5 was identified among a panel of genes associated with high EMT metagene scores, implicating it in tumorigenic processes such as metastasis and therapeutic resistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Although its precise biological role has yet to be fully elucidated, by analogy with CALHM1 its channel properties are likely governed by both membrane voltage and extracellular Ca²⁺ levels, enabling it to modulate intercellular signaling via ATP and ion permeation. This notion is further underlined by the broader importance of calcium‐dependent channels and related proteins in diverse physiological contexts—including innate immune cell activation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", musculoskeletal pain in myopathies"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", and renal pathology"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "—as well as in the regulation of muscle and connective tissue homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Collectively, these studies suggest that CALHM5, by virtue of its structural and regulatory similarities to CALHM1, might play a pivotal role in Ca²⁺-dependent signaling cascades that influence cellular excitability, tissue remodeling, and disease progression.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, while further research is needed to define its unique functions, current evidence positions CALHM5 as a candidate regulator of ATP and ion flux in cells—potentially contributing to processes ranging from neuronal communication and sensory signaling to the modulation of tumor cell behavior.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Eijaz Ahmed Bhat, Nasreena Sajjad, Saeed Banawas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human CALHM5: Insight in large pore lipid gating ATP channel and associated neurological pathologies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biochem (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11010-021-04198-y"}], "href": "https://doi.org/10.1007/s11010-021-04198-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34089472"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34089472"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Zhongming Ma, Jessica E Tanis, Akiyuki Taruno, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Calcium homeostasis modulator (CALHM) ion channels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pflugers Arch (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00424-015-1757-6"}], "href": "https://doi.org/10.1007/s00424-015-1757-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26603282"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26603282"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Dandan Li, Zhi Liu, Xiaorong Ding, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AEBP1 Is One of the Epithelial-Mesenchymal Transition Regulatory Genes in Colon Adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Res Int (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2021/3108933"}], "href": "https://doi.org/10.1155/2021/3108933"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34938806"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34938806"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Takashi Ebihara, Masahiro Azuma, Hiroyuki Oshiumi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a polyI:C-inducible membrane protein that participates in dendritic cell-mediated natural killer cell activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20091573"}], "href": "https://doi.org/10.1084/jem.20091573"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21059856"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21059856"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Rabih Moshourab, Vinko Palada, Stefanie Grunwald, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Molecular Signature of Myalgia in Myotonic Dystrophy 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EBioMedicine (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ebiom.2016.03.017"}], "href": "https://doi.org/10.1016/j.ebiom.2016.03.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27322473"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27322473"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Andrew S Potter, Keri Drake, Eric W Brunskill, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A bigenic mouse model of FSGS reveals perturbed pathways in podocytes, mesangial cells and endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0216261"}], "href": "https://doi.org/10.1371/journal.pone.0216261"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31461442"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31461442"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ali Ali, Rafet Al-Tobasei, Daniela Lourenco, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-Wide Association Study Identifies Genomic Loci Affecting Filet Firmness and Protein Content in Rainbow Trout."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fgene.2019.00386"}], "href": "https://doi.org/10.3389/fgene.2019.00386"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31130980"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31130980"}]}]}]}