2',3'-cyclic-nucleotide 3'-phosphodiesterase

2',3'-Cyclic-nucleotide 3'-phosphodiesterase (CNP) is a myelin-associated enzyme that catalyzes the phosphodiester hydrolysis of 2',3'-cyclic nucleotides to 2'-nucleotides (UniProt: P09543). In mitochondria, CNP regulates the mitochondrial permeability transition pore and participates in cell death mechanisms; it also functions as an antiviral factor against SARS-CoV-2 and HIV-1 virions.

CNP is expressed in myelin-forming tissues and is implicated in white matter integrity. Mutations in CNP cause hypomyelinating leukodystrophy 20 (HLD20; MIM 619071), a severe autosomal recessive neurodegenerative disorder characterized by progressive loss of motor, language, and cognitive function beginning in early childhood (UniProt: P09543).

CNP is significantly downregulated in Alzheimer's disease brain tissue compared to age-matched controls, with a mean log₂ fold-change of −0.68 across analyzed subcellular fractions (Chaparral AD proteomics). This reduction may reflect compromised myelin integrity and mitochondrial dysfunction in AD pathology.