{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe provided studies shed light on a key regulator of inositol phosphate signaling—although noted as INPP5A rather than MIR3652—which is critical for neuronal calcium homeostasis. In the first study, mutant TATA box-binding protein in spinocerebellar ataxia 17 impairs SP1‐mediated transcription, leading to a marked reduction in INPP5A levels in the cerebellum. This loss disrupts the delicate balance of inositol 1,4,5-trisphosphate (IP3) metabolism, results in abnormal calcium mobilization, and predisposes cerebellar Purkinje cells to degeneration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "Disruption of INPP5A function is also implicated in neurodevelopmental and psychiatric conditions. The second study describes a microduplication affecting part of the INPP5A gene in a family with childhood‐onset schizophrenia and autism spectrum disorder. Altered dosage of INPP5A is proposed to perturb intracellular calcium signals essential for dendritic spine morphogenesis, suggesting a molecular link between inositol phosphate metabolism and the pathophysiology of these disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "In summary, both studies converge on the importance of proper INPP5A function for neuronal integrity. By tightly regulating the levels of IP3 through its phosphatase activity, INPP5A helps maintain intracellular calcium equilibrium; its dysregulation—whether through transcriptional downregulation or gene duplication—can contribute to region-specific neurodegeneration as well as to neuropsychiatric manifestations."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Qiong Liu, Shanshan Huang, Peng Yin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cerebellum-enriched protein INPP5A contributes to selective neuropathology in mouse model of spinocerebellar ataxias type 17."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-020-14931-8"}], "href": "https://doi.org/10.1038/s41467-020-14931-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32107387"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32107387"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Arnaud Fernandez, Małgorzata Drozd, Susanne Thümmler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel microduplication in INPP5A segregates with schizophrenia spectrum disorder in the family of a patient with both childhood onset schizophrenia and autism spectrum disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.62155"}], "href": "https://doi.org/10.1002/ajmg.a.62155"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33720513"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33720513"}]}]}]}