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Diphosphoinositol polyphosphate phosphohydrolase 1 (DIPP1), also known as NUDT3, is a member of the Nudix hydrolase superfamily that specifically hydrolyzes inositol pyrophosphates (PP-InsPs), such as 5-IP7 and IP8 (UniProt P53370). These molecules are high-energy signaling metabolites that regulate diverse cellular processes, including vesicle trafficking, DNA repair, and phosphate homeostasis (Safrany et al., 1998). By controlling the turnover of these pyrophosphates, DIPP1 acts as a critical regulator of intracellular signaling and energy sensing (Shears, 2009). Genetic studies, including large-scale GWAS, have strongly linked NUDT3 variants to body mass index (BMI) and metabolic health, suggesting its involvement in obesity and insulin sensitivity (Locke et al., 2015). Additionally, DIPP1 has been implicated in cancer cell migration and survival, highlighting its potential as a therapeutic target in oncology (Hidaka et al., 2016). While there are currently no FDA-approved drugs specifically targeting DIPP1, it remains a significant subject of research for metabolic and neoplastic diseases (UniProt P53370; Hidaka et al., 2016).
Hydrolysis of the pyrophosphate bond in diphosphoinositol polyphosphates (e.g., 5-IP7, IP8) to regulate their intracellular concentrations and downstream signaling (UniProt P53370; Safrany et al., 1998).
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