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5'-Nucleotidase, cytosolic IA (NT5C1A) is an intracellular enzyme of the phosphatase family that dephosphorylates nucleoside monophosphates—primarily AMP—into nucleosides and inorganic phosphate, thereby regulating nucleotide and energy metabolism[1][2][3][5][6]. NT5C1A plays essential roles in modulating the cellular AMP/ATP ratio, promoting AMP-activated protein kinase (AMPK) activation, altering glucose metabolism, and lipid oxidation. It is highly relevant in the context of autoimmune muscle disease as a dominant autoantigen in sporadic inclusion body myositis (sIBM), where anti-NT5C1A autoantibodies serve as a diagnostic biomarker linked to disease severity[1]. In oncology, overexpression of NT5C1A mediates resistance to nucleoside analog chemotherapeutics, notably gemcitabine, in pancreatic cancer by reducing levels of drug metabolites within cancer cells[1][5]. The enzyme’s enzymatic function also affects adenosine regulation in tissues such as the heart under ischemic conditions[6]. In summary, NT5C1A is a cytosolic phosphatase with a central role in nucleotide metabolism, immune pathophysiology, and drug response modulation.
Drug inactivation (by dephosphorylation of nucleoside analogs, reducing their cytotoxic effect in cancer); Modulation of nucleotide pools (can affect cellular energy status and metabolic adaptation)
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