{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nA large body of work has established the critical role of the PAS‐domain kinase (PASK/PASKIN) as a nutrient and bioenergetic sensor that orchestrates multiple aspects of metabolic homeostasis. In pancreatic beta‐cells, PASK modulates insulin gene transcription and protein stability by phosphorylating key regulators (for example, indirectly by inactivating GSK3β to prevent PDX-1 degradation), thereby influencing insulin secretion under fluctuating glucose levels (see, for example, studies reporting on metabolic syndrome and beta‐cell glucolipotoxicity). PASK’s activity is also essential in other tissues, where it regulates hepatic glucose handling and lipogenesis during fasting and refeeding, modulates hypothalamic energy-sensing pathways (including AMPK/mTOR signaling) in response to nutrient and hormonal cues such as GLP-1, and even impacts ventilatory responses to hypoxia. Moreover, PASK appears to influence mitochondrial homeostasis and cell repair during aging as well as differentiation competence in stem cells via its regulated nuclear translocation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn parallel, several studies have detailed the function of the synaptic cell-adhesion molecule LRRTM3 in neural circuit formation. LRRTM3 plays a pivotal role in the development and functional modulation of excitatory synapses – particularly within the hippocampus – by regulating the density and strength of synaptic contacts. LRRTM3 interacts directly with both the amyloid precursor protein (APP) and the protease BACE1 in early endosomes, suggesting that its modulation of APP processing may be relevant to Alzheimer’s disease risk. Furthermore, splice variant–dependent interactions with presynaptic neurexins add a further layer of regulation critical for synaptogenic activity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, emerging data highlight that transcriptomic alterations – including rare fusion transcripts – may also contribute to tumorigenesis, as illustrated in metastatic colorectal carcinoma. Although not directly linked to PASK or LRRTM3 functions, these findings add to the complex landscape of gene regulation in human disease and potentially offer novel diagnostic and therapeutic targets."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Dörthe M Katschinski, Hugo H Marti, Klaus F Wagner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeted disruption of the mouse PAS domain serine/threonine kinase PASKIN."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.23.19.6780-6789.2003"}], "href": "https://doi.org/10.1128/MCB.23.19.6780-6789.2003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12972598"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12972598"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Emanuela Borter, Markus Niessen, Richard Zuellig, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Ventilatory responses to acute and chronic hypoxia are altered in female but not male Paskin-deficient mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Regul Integr Comp Physiol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpregu.00876.2007"}], "href": "https://doi.org/10.1152/ajpregu.00876.2007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18509100"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18509100"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ghislaine Fontés, Meriem Semache, Derek K Hagman, et al. 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