{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have revealed that YIPF5 plays essential roles in intracellular membrane trafficking with significant clinical implications. Loss‐of‐function mutations in YIPF5 disrupt the normal flow between the endoplasmic reticulum (ER) and Golgi apparatus, leading to proinsulin retention, marked ER stress, and consequent β‐cell failure. This defect underlies a congenital syndrome characterized by neonatal/early‐onset diabetes, severe microcephaly, and epilepsy, while additional findings indicate that YIPF5 also acts as a positive regulator of innate immunity by facilitating STING recruitment to COPII-coated vesicles for proper signaling in response to DNA pathogens."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the cellular level, YIPF5 is a member of the Yip1p/Yif1p protein family and localizes predominantly to the ER–Golgi intermediate compartment and cis-Golgi. Its association with YIF1A is critical for maintaining the Golgi structure and ensuring efficient recycling between the ER and Golgi. Systematic analyses of YIPF-family proteins have further categorized YIPF5 as a cis-Golgi-resident factor, underscoring its importance in preserving endomembrane system dynamics."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, chromosomal studies have demonstrated that structural rearrangements affecting the YIPF5 locus can result in a position effect, which impairs spermatogenesis and is associated with male infertility. This expanding spectrum of YIPF5 function—from secretory trafficking and immune regulation to the maintenance of Golgi organization and implications in reproductive biology—highlights its broad physiological significance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yong Ran, Mei-Guang Xiong, Zhi-Sheng Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "YIPF5 Is Essential for Innate Immunity to DNA Virus and Facilitates COPII-Dependent STING Trafficking."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1900387"}], "href": "https://doi.org/10.4049/jimmunol.1900387"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31391232"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31391232"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Elisa De Franco, Maria Lytrivi, Hazem Ibrahim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "YIPF5 mutations cause neonatal diabetes and microcephaly through endoplasmic reticulum stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI141455"}], "href": "https://doi.org/10.1172/JCI141455"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33164986"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33164986"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yumi Yoshida, Kurumi Suzuki, Akitsugu Yamamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "YIPF5 and YIF1A recycle between the ER and the Golgi apparatus and are involved in the maintenance of the Golgi structure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2008.07.023"}], "href": "https://doi.org/10.1016/j.yexcr.2008.07.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18718466"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18718466"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Tilen Kranjc, Eugene Dempsey, Gerard Cagney, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional characterisation of the YIPF protein family in mammalian cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Histochem Cell Biol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00418-016-1527-3"}], "href": "https://doi.org/10.1007/s00418-016-1527-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27999994"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27999994"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Dezső David, Joana Fino, Renata Oliveira, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Balanced chromosomal rearrangements implicate YIPF5 and SPATC1L in non-obstructive oligoasthenozoospermia and oligozoospermia and of a derivative chromosome 22 in recurrent miscarriage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2023.147737"}], "href": "https://doi.org/10.1016/j.gene.2023.147737"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37625567"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37625567"}]}]}]}