CNPase is a myelin-associated enzyme that makes up 4% of total CNS myelin protein, and is thought to undergo significant age-associated changes. It is named for its ability to catalyze the phosphodiesterhydrolysis of 2',3'-cyclic nucleotides to 2'-nucleotides, though a cohesive understanding of its specific physiologic functions are still ambiguous.
Structural studies have revealed that four classes of CNPases belong to one protein superfamily. CNPase's catalytic core consists of three alpha-helices and nine beta-strands. The proposed mechanism of CNPases phosphodiesterase catalytic activity is similar to the second step of the reaction mechanism for RNase A.
CNPase is expressed exclusively by oligodendrocytes in the CNS, and the appearance of CNPase seems to be one of the earliest events of oligodendrocyte differentiation. CNPase is thought to play a critical role in the events leading up to myelination.
CNPase also associates with microtubules in brain tissue and FRTL-5 thyroid cells, and is reported to have microtubule-associated protein-like activity (MAP; see MAP2), being able to catalyze microtubule formation at low molar ratios. Deletion of the C-terminus of CNPase or phosphorylation abolish the catalytic activity of microtubule formation. CNPase can link tubulin to cellular membranes, and might be involved in the regulation cytoplasmic microtubule distribution.
Interestingly, CNPase has also been demonstrated to inhibit the replication of HIV-1 and other primate lentiviruses by binding the retroviral Gag protein and inhibiting the genesis of nascent viral particles. Whether this is a biological function of CNPase or a coincidental activity remains unclear 
^Sakamoto Y, Tanaka N, Ichimiya T, Kurihara T, Nakamura KT (February 2005). "Crystal structure of the catalytic fragment of human brain 2',3'-cyclic-nucleotide 3'-phosphodiesterase". J. Mol. Biol.346 (3): 789–800. doi:10.1016/j.jmb.2004.12.024. PMID15713463.
^Kasama-Yoshida H, Tohyama Y, Kurihara T, Sakuma M, Kojima H, Tamai Y (October 1997). "A comparative study of 2',3'-cyclic-nucleotide 3'-phosphodiesterase in vertebrates: cDNA cloning and amino acid sequences for chicken and bullfrog enzymes". J. Neurochem.69 (4): 1335–42. doi:10.1046/j.1471-4159.1997.69041335.x. PMID9326261.
^Gravel M, Peterson J, Yong VW, Kottis V, Trapp B, Braun PE (June 1996). "Overexpression of 2',3'-cyclic nucleotide 3'-phosphodiesterase in transgenic mice alters oligodendrocyte development and produces aberrant myelination". Mol. Cell. Neurosci.7 (6): 453–66. doi:10.1006/mcne.1996.0033. PMID8875429.
Drummond GI, Iyer NT and Keith J (1962). "Hydrolysis of ribonucleoside 2',3'-cyclic phosphates by a diesterase from brain". J. Biol. Chem.237: 3535–3539.
Helfman DM, Kuo JF (1982). "A homogeneous cyclic CMP phosphodiesterase hydrolyzes both pyrimidine and purine cyclic 2':3'- and 3':5'-nucleotides". J. Biol. Chem.257 (2): 1044–7. PMID6274851.
Helfman DM, Shoji M, Kuo JF (1981). "Purification to homogeneity and general properties of a novel phosphodiesterase hydrolyzing cyclic CMP and cyclic AMP". J. Biol. Chem.256 (12): 6327–34. PMID6263914.
Thompson RJ (1992). "2',3'-cyclic nucleotide-3'-phosphohydrolase and signal transduction in central nervous system myelin.". Biochem. Soc. Trans.20 (3): 621–6. PMID1385234.
Leroy MJ, Dumler I, Lugnier C, et al. (1992). "A new peptide (1150Da) selectively activates the calcium-calmodulin sensitive isoform of cyclic nucleotide phosphodiesterase from human myometrium.". Biochem. Biophys. Res. Commun.184 (2): 700–5. doi:10.1016/0006-291X(92)90646-3. PMID1315529.
Staugaitis SM, Bernier L, Smith PR, Colman DR (1990). "Expression of the oligodendrocyte marker 2'3'-cyclic nucleotide 3'-phosphodiesterase in non-glial cells.". J. Neurosci. Res.25 (4): 556–60. doi:10.1002/jnr.490250413. PMID2161933.
Agrawal HC, Sprinkle TJ, Agrawal D (1990). "2',3'-cyclic nucleotide-3'-phosphodiesterase in the central nervous system is fatty-acylated by thioester linkage.". J. Biol. Chem.265 (20): 11849–53. PMID2164018.
Kurihara T, Takahashi Y, Nishiyama A, Kumanishi T (1988). "cDNA cloning and amino acid sequence of human brain 2',3'-cyclic-nucleotide 3'-phosphodiesterase.". Biochem. Biophys. Res. Commun.152 (2): 837–42. doi:10.1016/S0006-291X(88)80114-1. PMID2835044.
Sprinkle TJ, McMorris FA, Yoshino J, DeVries GH (1985). "Differential expression of 2':3'-cyclic nucleotide 3'-phosphodiesterase in cultured central, peripheral, and extraneural cells.". Neurochem. Res.10 (7): 919–31. doi:10.1007/BF00964629. PMID2995854.
Sheedlo HJ, Doran JE, Sprinkle TJ (1984). "An investigation of 2':3'-cyclic nucleotide 3'-phosphodiesterase (EC 126.96.36.199, CNP) in peripheral blood elements and CNS myelin.". Life Sci.34 (18): 1731–7. doi:10.1016/0024-3205(84)90572-1. PMID6328143.
Monoh K, Kurihara T, Takahashi Y, et al. (1993). "Structure, expression and chromosomal localization of the gene encoding human 2',3'-cyclic-nucleotide 3'-phosphodiesterase.". Gene129 (2): 297–301. doi:10.1016/0378-1119(93)90283-9. PMID8392017.
Löbbert RW, Winterpacht A, Seipel B, Zabel BU (1997). "Molecular cloning and chromosomal assignment of the human homologue of the rat cGMP-inhibited phosphodiesterase 1 (PDE3A)--a gene involved in fat metabolism located at 11p 15.1.". Genomics37 (2): 211–8. doi:10.1006/geno.1996.0544. PMID8921398.
Stricker R, Kalbacher H, Reiser G (1997). "The epitope recognized by a monoclonal antibody in the myelin-associated protein CNP.". Biochem. Biophys. Res. Commun.237 (2): 266–70. doi:10.1006/bbrc.1997.7125. PMID9268698.
O'Neill RC, Braun PE (2000). "Selective synthesis of 2',3'-cyclic nucleotide 3'-phosphodiesterase isoform 2 and identification of specifically phosphorylated serine residues.". J. Neurochem.74 (2): 540–6. doi:10.1046/j.1471-4159.2000.740540.x. PMID10646504.
Zauli G, Milani D, Mirandola P, et al. (2001). "HIV-1 Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3-kinase/AKT/cyclic nucleoside phosphodiesterase pathway.". FASEB J.15 (2): 483–91. doi:10.1096/fj.00-0354com. PMID11156964.
Davidoff MS, Middendorff R, Köfüncü E, et al. (2002). "Leydig cells of the human testis possess astrocyte and oligodendrocyte marker molecules.". Acta Histochem.104 (1): 39–49. doi:10.1078/0065-1281-00630. PMID11993850.
Basrur V, Yang F, Kushimoto T, et al. (2003). "Proteomic analysis of early melanosomes: identification of novel melanosomal proteins.". J. Proteome Res.2 (1): 69–79. doi:10.1021/pr025562r. PMID12643545.
Kozlov G, Lee J, Elias D, et al. (2003). "Structural evidence that brain cyclic nucleotide phosphodiesterase is a member of the 2H phosphodiesterase superfamily.". J. Biol. Chem.278 (46): 46021–8. doi:10.1074/jbc.M305176200. PMID12947117.