{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPMF1‐BGLAP appears to serve as an integrative regulator of protein S‐palmitoylation, a reversible lipid modification mediated by zinc finger DHHC‐domain acyltransferases. Multiple studies have shown that enzymes such as HIP14 and HIP14L promote the palmitoylation of key neuronal substrates—including huntingtin and SNAP25—ensuring proper synaptic function and Mg²⁺ transport. These processes are essential for maintaining neuronal homeostasis, and defects in PAT activity have been linked to neurodegenerative phenotypes reminiscent of Huntington’s disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its neurological roles, the PMF1‐BGLAP network is implicated in skeletal development and skin homeostasis. Loss‐of‐function mutations in PAT genes such as Zdhhc13 have been associated with delayed ossification, reduced bone mineral density, and decreased osteocalcin expression due to impaired palmitoylation (for example, of MT1‐MMP). Moreover, disrupted PAT activity has been linked to aberrant BMP signaling during early embryogenesis and contributes to skin abnormalities—including hypotrichosis, epidermal hyperplasia, and enhanced carcinogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, PMF1‐BGLAP–linked regulatory pathways extend to the control of mitochondrial dynamics, anxiety‐related behaviors, and the integrity of skin barrier functions. Deficiencies in ZDHHC13 affect the palmitoylation of proteins such as Drp1—thereby disrupting mitochondrial fission–fusion balance and culminating in altered neurotransmission and motor coordination—while also predisposing the skin to barrier defects and heightened inflammatory responses upon microbial challenge. These diverse roles highlight the significance of proper palmitoylation in maintaining physiological homeostasis across multiple tissues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Angela Goytain, Rochelle M Hines, Gary A Quamme "}, {"type": "b", "children": [{"type": "t", "text": "Huntingtin-interacting proteins, HIP14 and HIP14L, mediate dual functions, palmitoyl acyltransferase and Mg2+ transport."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M801469200"}], "href": "https://doi.org/10.1074/jbc.M801469200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18794299"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18794299"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Amir N Saleem, Yen-Hui Chen, Hwa Jin Baek, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mice with alopecia, osteoporosis, and systemic amyloidosis due to mutation in Zdhhc13, a gene coding for palmitoyl acyltransferase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1000985"}], "href": "https://doi.org/10.1371/journal.pgen.1000985"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20548961"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20548961"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Liza M Sutton, Shaun S Sanders, Stefanie L Butland, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Zinc finger DHHC-type containing 13 regulates fate specification of ectoderm and mesoderm cell lineages by modulating Smad6 activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stem Cells Dev (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/scd.2014.0068"}], "href": "https://doi.org/10.1089/scd.2014.0068"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24702307"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24702307"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Shaun S Sanders, Juan Hou, Liza M Sutton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Huntingtin interacting proteins 14 and 14-like are required for chorioallantoic fusion during early placental development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ydbio.2014.11.018"}], "href": "https://doi.org/10.1016/j.ydbio.2014.11.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25478910"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25478910"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Kimon Lemonidis, Maria C Sanchez-Perez, Luke H Chamberlain "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a Novel Sequence Motif Recognized by the Ankyrin Repeat Domain of zDHHC17/13 S-Acyltransferases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M115.657668"}], "href": "https://doi.org/10.1074/jbc.M115.657668"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26198635"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26198635"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Carlos J Perez, Lars Mecklenburg, Jean Jaubert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased Susceptibility to Skin Carcinogenesis Associated with a Spontaneous Mouse Mutation in the Palmitoyl Transferase Zdhhc13 Gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jid.2015.314"}], "href": "https://doi.org/10.1038/jid.2015.314"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26288350"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26288350"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Li-Ying Chen, Hsin-Fang Yang-Yen, Chun-Chou Tsai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein Palmitoylation by ZDHHC13 Protects Skin against Microbial-Driven Dermatitis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jid.2016.12.011"}], "href": "https://doi.org/10.1016/j.jid.2016.12.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28017833"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28017833"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Eleonora Napoli, Gyu Song, Siming Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Zdhhc13-dependent Drp1 S-palmitoylation impacts brain bioenergetics, anxiety, coordination and motor skills."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-017-12889-0"}], "href": "https://doi.org/10.1038/s41598-017-12889-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29038583"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29038583"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Li-Ying Chen, Kuo-Ray Lin, Yi-Ju Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Palmitoyl Acyltransferase Activity of ZDHHC13 Regulates Skin Barrier Development Partly by Controlling PADi3 and TGM1 Protein Stability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jid.2019.09.017"}], "href": "https://doi.org/10.1016/j.jid.2019.09.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31669413"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31669413"}]}]}]}