Cytosolic purine 5'-nucleotidase

Cytosolic purine 5'-nucleotidase (NT5C2) is a broad-specificity nucleotidase that catalyzes dephosphorylation of purine nucleoside monophosphates and possesses phosphotransferase activity, thereby regulating intracellular purine nucleoside and nucleotide pools (UniProt: P49902). The enzyme shows highest activity toward inosine monophosphate (IMP) and guanosine monophosphate (GMP), with lower efficiency toward pyrimidine substrates. It is expressed as a 561-amino acid cytosolic protein with a molecular mass of approximately 65 kDa.

NT5C2 is associated with spastic paraplegia 45 (SPG45), an autosomal recessive neurodegenerative disorder characterized by progressive lower-limb weakness and spasticity; some patients also present with intellectual disability and learning difficulties (UniProt: P49902). The protein's role in nucleotide metabolism suggests broader relevance to neuronal function and cellular energy homeostasis, though tissue-specific expression patterns are not detailed in available records.

In Alzheimer's disease, NT5C2 is upregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change 0.58, Chaparral AD proteomics). This elevation was detected in a subcellular fractionation proteomics study of human brain, suggesting potential involvement in AD-associated metabolic or signaling dysregulation, though the functional consequence remains to be determined.