{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTRAPPC9 is a key component of the transport protein particle (TRAPP) complexes that function as multimeric guanine nucleotide exchange factors regulating the GTPases Ypt1 in yeast and RAB1 in mammals. By participating in several distinct TRAPP assemblies, TRAPPC9 helps coordinate vesicle tethering and intracellular membrane trafficking events—including endoplasmic reticulum to Golgi transport, intra‐Golgi traffic, and autophagy—and may also influence the association of COPII vesicles with microtubules."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in membrane trafficking, TRAPPC9 (also known as NIBP) functions as an enhancer of the NF‑κB signaling pathway by physically interacting with key kinases such as NIK and IKKβ. This interaction amplifies cytokine‐induced NF‑κB activation, which is critical for neuronal differentiation, survival, and proper brain development. Genetic studies in diverse populations have identified truncating and splice site mutations in TRAPPC9 that result in autosomal recessive intellectual disability; affected individuals frequently present with features such as postnatal microcephaly, cerebral white matter hypoplasia, impaired axonal connectivity, obesity, and severe speech impairment. Structural and protein–protein docking analyses further suggest that disruption of TRAPPC9’s interactions may underlie the variability observed in these neurodevelopmental syndromes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging evidence extends the functional repertoire of TRAPPC9 beyond neurodevelopment to include roles in oncogenesis and chemoresistance. Through its regulation of the canonical NF‑κB pathway, TRAPPC9 (NIBP) modulates the expression of matrix metalloproteinases and epithelial–mesenchymal transition markers, thereby promoting tumor cell proliferation, invasion, and metastasis in colorectal and gastric cancers. Moreover, common genetic variants and epigenetic modifications of TRAPPC9 have been implicated in neuropsychiatric conditions such as attention deficit hyperactivity disorder, suggesting that subtle alterations in its expression can affect both brain metabolism and developmental outcomes. Together, these studies indicate that TRAPPC9 serves as a multifunctional protein integrating vesicular trafficking, inflammatory signaling, and transcriptional regulation across diverse biological systems."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jemima Barrowman, Deepali Bhandari, Karin Reinisch, et al. 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