Spleen exonuclease (, 3'-exonuclease, spleen phosphodiesterase, 3'-nucleotide phosphodiesterase, phosphodiesterase II) is an enzyme. This enzyme catalyses the following chemical reaction
<div align=center><small>Exonucleolytic cleavage in the 5'- to 3'-direction to yield nucleoside 3'-phosphates (exonuclease type b)</small></div>
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.