Spleen exonuclease (, 3'-exonuclease, spleen phosphodiesterase, 3'-nucleotide phosphodiesterase, phosphodiesterase II) is an enzyme. This enzyme catalyses the following chemical reaction

Exonucleolytic cleavage in the 5'- to 3'-direction to yield nucleoside 3'-phosphates (exonuclease type b)

This enzyme has a preference for single-stranded substrate.

PLD3 and/or PLD4 might be the genes encoding spleen exonuclease, as they have similar substrate specificity and tissue distribution.

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