{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNeuroplastin (NPTN) functions as a versatile membrane protein that supports both cell survival and intercellular signalling. In non‐neuronal cells, NPTN acts as a chaperone by guiding proteins such as Xkr8 to the plasma membrane where they mediate apoptotic phospholipid scrambling, and it serves as an indispensable subunit of plasma membrane Ca²⁺ ATPases (PMCAs) to enhance Ca²⁺ clearance and maintain cellular Ca²⁺ homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nWithin the nervous system, NPTN (present as the isoforms Np65 and Np55) is a critical cell adhesion molecule that regulates neurite outgrowth, synaptic formation, and plasticity. By interacting with a diverse array of protein partners—including fibroblast growth factor receptors, glutamate receptors, and various GABA_A receptor subunits—NPTN controls the trafficking and membrane localization of these key synaptic components, thereby influencing both excitatory and inhibitory circuit functions. Variations in expression levels, as well as genetic polymorphisms in regulatory regions upstream of the NPTN gene, have been associated with alterations in cortical thickness, hemispheric asymmetry, and ultimately with differences in intellectual ability. Studies using neuron-selective ablation models further emphasize its role in regulating intracellular Ca²⁺ dynamics, synaptic activity, and overall cognitive function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in normal physiology, NPTN is implicated in disease processes. Genetic variants in its regulatory regions have been linked to an increased susceptibility to schizophrenia, suggesting that even subtle perturbations of NPTN expression can impact neuropsychiatric function. Moreover, the NPTNβ isoform serves as a receptor for extracellular S100A8/A9 proteins, activating downstream signaling cascades (involving TRAF2/RAS, NFIA/NFIB, and SPDEF) that promote anchorage-independent growth, motility, and invasiveness in cancer cells, particularly in lung cancer, thereby contributing to cancer disseminative progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jun Suzuki, Eiichi Imanishi, Shigekazu Nagata "}, {"type": "b", "children": [{"type": "t", "text": "Xkr8 phospholipid scrambling complex in apoptotic phosphatidylserine exposure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1610403113"}], "href": "https://doi.org/10.1073/pnas.1610403113"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27503893"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27503893"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Deshun Gong, Ximin Chi, Kang Ren, et al. 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