{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CALHM6 (also referred to as FAM26F) is a transmembrane protein that appears to play a dual role in ion transport and immune cell signaling. Structurally, CALHM6 contains a conserved Ca_hom_mod domain and is predicted to function as a cation channel. Recent cryo‐electron microscopy studies have revealed that, unlike its paralog CALHM4 which forms cylindrical pores, CALHM6 adopts a distinct “conical” pore conformation that narrows at the intracellular side; this unique geometry is likely to alter the lipid distribution within the channel and could have important functional consequences for ion permeation and cellular signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its biophysical properties, CALHM6 is emerging as an important immunomodulator. Its expression is upregulated in response to immune stimulants—including polyinosinic‐polycytidylic acid, lipopolysaccharide, interferon‐γ, and tumor necrosis factor‐α—which suggests that CALHM6 may facilitate intercellular communication during inflammatory responses. In fact, studies in the context of kidney diseases such as steroid‐sensitive nephrotic syndrome have identified CALHM6/FAM26F among immune‐related genes that associate with disease susceptibility and progression, highlighting its potential role as a biomarker for immunologically driven pathology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, independent analyses of FAM26F expression in various immune contexts have demonstrated that this molecule is implicated in the activation and functional cross‐talk of natural killer cells and dendritic cells, reinforcing the concept that CALHM6 participates in orchestrating innate immune responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Taken together, CALHM6 is a uniquely structured calcium‐ and voltage‐gated cation channel with significant roles in regulating immune cell interactions and inflammatory responses. Its ability to switch conformations may serve as a molecular mechanism to modulate intercellular signaling events, making it an attractive target for further research into therapeutic interventions addressing immune‐mediated diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Katarzyna Drożdżyk, Marta Sawicka, Maria-Isabel Bahamonde-Santos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cryo-EM structures and functional properties of CALHM channels of the human placenta."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.55853"}], "href": "https://doi.org/10.7554/eLife.55853"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32374262"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32374262"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Tomoko Horinouchi, Kandai Nozu, Kazumoto Iijima "}, {"type": "b", "children": [{"type": "t", "text": "An updated view of the pathogenesis of steroid-sensitive nephrotic syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pediatr Nephrol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00467-021-05401-4"}], "href": "https://doi.org/10.1007/s00467-021-05401-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35006356"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35006356"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Uzma Malik, Aneela Javed, Amjad Ali, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural and functional annotation of human FAM26F: A multifaceted protein having a critical role in the immune system."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2016.10.029"}], "href": "https://doi.org/10.1016/j.gene.2016.10.029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27784631"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27784631"}]}]}]}