{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The KICSTOR complex—composed of KPTN, ITFG2, C12orf66, and SZT2—acts as a critical lysosome‐associated negative regulator of mTORC1 signaling. Under conditions of nutrient limitation (e.g., amino acid or glucose deprivation), KICSTOR recruits the GATOR1 complex to the lysosomal membrane, thereby facilitating GATOR1’s ability to inactivate the Rag GTPases and prevent mTORC1 activation. Loss or mutation of key KICSTOR components, particularly SZT2, disrupts this regulatory mechanism, resulting in constitutive mTORC1 activity even under nutrient‐poor conditions—a scenario linked to neurodevelopmental disorders such as epilepsy and developmental delay."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Thus, KICSTOR functions as an essential metabolic gatekeeper by integrating nutrient signals at the lysosome and ensuring proper mTORC1 regulation to maintain cellular metabolic homeostasis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Rachel L Wolfson, Lynne Chantranupong, Gregory A Wyant, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to regulate mTORC1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature21423"}], "href": "https://doi.org/10.1038/nature21423"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28199306"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28199306"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yuji Nakamura, Kohji Kato, Naomi Tsuchida, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Constitutive activation of mTORC1 signaling induced by biallelic loss-of-function mutations in SZT2 underlies a discernible neurodevelopmental disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0221482"}], "href": "https://doi.org/10.1371/journal.pone.0221482"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31430354"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31430354"}]}]}]}