{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nZDHHC21, a palmitoyl acyltransferase responsible for the reversible lipid modification of proteins, has emerged as a critical regulator of cellular signaling and tissue homeostasis. In skin, a loss‐of‐function mutation in Zdhhc21 disrupts normal palmitoylation of key signaling molecules such as Fyn, leading to localized delays in hair shaft differentiation and widespread epidermal abnormalities, thus underscoring its importance in the regulation of developmental cues and tissue integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn vascular and intestinal tissues, ZDHHC21’s enzymatic activity is equally pivotal. In the vasculature, mice expressing a nonfunctional form of ZDHHC21 display impaired receptor palmitoylation that alters vascular reactivity, while in the gut, inflammatory stimuli induce ZDHHC21 expression and an increase in overall protein palmitoylation—mechanisms that contribute to epithelial hyperpermeability after thermal injury. These insights not only demonstrate its role in modulating vasomotor responses but also highlight ZDHHC21 as a potential target for reducing burn-induced barrier dysfunction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nWithin the immune system, ZDHHC21 governs T cell receptor (TCR) signaling by mediating the S-acylation of proximal signaling proteins. Its activity is Ca2+/calmodulin-dependent and essential for the initiation of T cell activation; disruption of ZDHHC21 impairs early TCR signals and prevents the proper differentiation of naïve T cells into Th1, Th2, and Th17 lineages. These findings delineate a previously unappreciated role for protein acyltransferases in orchestrating adaptive immunity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond these roles, ZDHHC21 is implicated in maintaining renal function during septic injury. By modulating the palmitoylation of receptors implicated in vascular tone—such as the alpha‐adrenergic receptor—ZDHHC21 influences renal perfusion and oxygenation. Loss of its function protects against the renal hemodynamic impairments typically observed during sepsis, suggesting that targeting its palmitoylation activity could offer new therapeutic avenues for ameliorating septic renal dysfunction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Pleasantine Mill, Angela W S Lee, Yuko Fukata, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Palmitoylation regulates epidermal homeostasis and hair follicle differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1000748"}], "href": "https://doi.org/10.1371/journal.pgen.1000748"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19956733"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19956733"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ethan P Marin, Levente Jozsef, Annarita Di Lorenzo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Protein Acyl Transferase ZDHHC21 Modulates α1 Adrenergic Receptor Function and Regulates Hemodynamics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/ATVBAHA.115.306942"}], "href": "https://doi.org/10.1161/ATVBAHA.115.306942"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26715683"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26715683"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "R J Haines, C Y Wang, C G Y Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeting palmitoyl acyltransferase ZDHHC21 improves gut epithelial barrier dysfunction resulting from burn-induced systemic inflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Gastrointest Liver Physiol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpgi.00145.2017"}], "href": "https://doi.org/10.1152/ajpgi.00145.2017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28838985"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28838985"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ying Fan, Bieerkehazhi Shayahati, Ritika Tewari, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of T cell receptor signaling by protein acyltransferase DHHC21."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11033-020-05691-1"}], "href": "https://doi.org/10.1007/s11033-020-05691-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32789573"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32789573"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Shayahati Bieerkehazhi, Ying Fan, Savannah J West, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ca2+-dependent protein acyltransferase DHHC21 controls activation of CD4+ T cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.258186"}], "href": "https://doi.org/10.1242/jcs.258186"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34080635"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34080635"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Xiaoyuan Yang, Ethan Zheng, Yonggang Ma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DHHC21 deficiency attenuates renal dysfunction during septic injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-021-89983-x"}], "href": "https://doi.org/10.1038/s41598-021-89983-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34045489"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34045489"}]}]}]}