RNASEH1 encodes ribonuclease H1, an endonuclease that specifically degrades the RNA component of RNA-DNA hybrids 1. The enzyme plays critical roles in both nuclear and mitochondrial processes. In the nucleus, RNASEH1 contributes to RNA polymerase II transcription termination by degrading R-loop structures at G-rich pause sites downstream of polyadenylation signals 2. RNASEH1 also regulates R-loops formed during active transcription at gene promoters, particularly those with G/C skew 3, and prevents transcription-replication collisions by facilitating R-loop resolution 4. Additionally, RNASEH1 promotes homologous recombination by resolving R-loops and facilitating recombinase recruitment during both mitotic DNA repair 5 and meiotic recombination 6. In mitochondria, RNASEH1 is essential for mtDNA replication, functioning as part of the mitochondrial replisome 7. Pathogenic variants in RNASEH1 cause progressive external ophthalmoplegia with mitochondrial DNA deletions (autosomal recessive 2), a mitochondrial DNA maintenance disorder characterized by mtDNA depletion and deletions 7. Recently, a non-coding RNASEH1 variant (rs7607888) has been associated with type 1 diabetes susceptibility, with demonstrated interaction with HLA alleles 8.