SLFN13 (Schlafen family member 13) is an endoribonuclease that functions as a key regulator of translational control and viral restriction. The protein exhibits specific RNA cleavage activity, targeting both transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs) 1. SLFN13 cleaves tRNAs at a precise site 11 nucleotides from the 3'-terminus at the acceptor stem, though it does not act on tRNA(Sec) 1. Structural analysis reveals a unique pseudo-dimeric U-pillow-shaped architecture in the N-terminal domain that may clamp base-paired RNAs 1. The protein localizes to the cytoplasm where it inhibits protein synthesis and restricts HIV-1 replication in a nucleolytic activity-dependent manner 1. SLFN13 belongs to the interferon-stimulated gene family and is upregulated by type I interferon signaling in immune cells 2. In cancer contexts, SLFN13 expression is associated with tumor progression, stemness, and immune infiltration in various malignancies including glioblastoma, lung squamous cell carcinoma, and gastric cancer 345. The protein's dual role in antiviral defense and cancer progression highlights its importance in cellular stress responses and translational regulation.