Ribonuclease which is part of an E2/17beta-estradiol-induced pro-apoptotic signaling pathway. E2 stabilizes the PDE3A/SLFN12 complex in the cytosol, promoting the dephosphorylation of SLFN12 and activating its pro-apoptotic ribosomal RNA/rRNA ribonuclease activity. This apoptotic pathway might be relevant in tissues with high concentration of E2 and be for instance involved in placenta remodeling (PubMed:31420216, PubMed:35104454, PubMed:34272366, PubMed:34707099). May play a role in cell differentiation (PubMed:30045019). Homodimer (PubMed:34272366). Interacts with PDE3A; direct low affinity interaction which is stimulated by binding of 17beta-estradiol/E2 to PDE3A and that positively regulates the ribonuclease activity of SLFN12 (PubMed:31420216, PubMed:35104454, PubMed:34272366, PubMed:34707099). Interacts with SERPINB12; as part of a pathway regulating cell differentiation (PubMed:30045019). Phosphorylation at Ser-368 and Ser-573 negatively regulates the ribonuclease activity (PubMed:35104454). Dephosphorylation is induced by the interaction with PDE3A and stimulates the rRNA ribonuclease activity (PubMed:35104454). Belongs to the Schlafen family. Subgroup II subfamily.