5'-nucleotidase, cytosolic II (NT5C2)

5'-nucleotidase, cytosolic II (NT5C2) is a cytosolic enzyme involved in purine nucleotide metabolism, catalyzing the dephosphorylation of inosine 5'-monophosphate (IMP) and guanosine 5'-monophosphate (GMP) to regulate intracellular purine nucleoside/nucleotide pools. It plays a key role in the inactivation of nucleoside analog pro-drugs (such as 6-mercaptopurine) used in chemotherapy, and activating mutations or over-expression of NT5C2 confer resistance to thiopurine drugs in acute lymphoblastic leukemia (ALL). Beyond its role in cancer, NT5C2 is implicated in a broad spectrum of metabolic and neuropsychiatric disorders, including hereditary spastic paraplegia, obesity, and schizophrenia, highlighting its role in cellular homeostasis and disease susceptibility. NT5C2 is an attractive therapeutic target in relapsed ALL; both genetic and pharmacologic inhibition restore chemosensitivity to thiopurines.

Other names

Cytosolic purine 5'-nucleotidaseNT5C2NT5BNT5CPPNT5cN-IISPG45SPG65Cytosolic IMP/GMP-specific 5'-nucleotidaseCytosolic nucleoside phosphotransferase 5'NHigh Km 5'-nucleotidasepurine 5'-nucleotidaseIMP-specific 5'-NTepididymis secretory sperm binding proteinspastic paraplegia 45 (autosomal recessive)

Dephosphorylation and inactivation of nucleoside analog pro-drugs (e.g., 6-MP, 6-thioguanine), reducing cytotoxic metabolite accumulation and conferring drug resistance; Inhibitors act by blocking NT5C2's nucleotidase activity, restoring sensitivity to nucleoside analog drugs