SLFN14 is a polysome-associated endoribonuclease that cleaves various RNA substrates including mRNAs and rRNAs in a magnesium- and manganese-dependent manner 1. The protein assembles into a stable homodimer featuring an RNase domain, SWADL domain, and helicase-like domain, but lacks functional helicase activity 12. SLFN14 specifically recognizes and cleaves RNAs containing short duplex regions such as hairpin RNAs and tRNAs 2, with substrate recognition occurring through phosphate backbone interactions rather than sequence-specificity 3. Functionally, SLFN14 regulates translation of codon-biased mRNAs through ribosome-dependent mechanisms and exhibits antiviral activity by inhibiting HIV-1 replication via translational repression and impairment of ribosomal frameshifting 24. In platelet biology, SLFN14 is essential for proper megakaryocyte maturation and proplatelet extension 5. Disease-causing missense mutations in SLFN14 cause inherited bleeding disorder, platelet-type 20, characterized by macrothrombocytopenia and platelet dysfunction 56. Pathogenic variants exhibit reduced protein expression through post-translational degradation and dysregulate megakaryocyte/platelet gene expression, with rRNA degradation triggering compensatory mTORC1-mediated ribosomal biogenesis 67.