DROSHA is a ribonuclease III endonuclease that catalyzes the initial nuclear processing step of microRNA biogenesis 1. As the catalytic component of the Microprocessor complex, DROSHA cleaves primary miRNA transcripts (pri-miRNAs) at positions ~11 nucleotides from the dsRNA-ssRNA junction to generate precursor miRNAs (pre-miRNAs) 2. This enzymatic activity requires precise stoichiometric balance with its binding partner DGCR8; dysregulation of this ratio impairs miRNA processing and triggers global miRNA dosage imbalance 3. Beyond canonical miRNA biogenesis, DROSHA exhibits additional functions including processing of non-miRNA hairpin-structured transcripts and involvement in pre-rRNA metabolism 4. Recent evidence reveals DROSHA's role in tumor suppression; loss of DROSHA in pineoblastoma accelerates tumorigenesis by derepressing cell cycle regulators 5. DROSHA dysregulation associates with multiple diseases including cancer, with polymorphisms linked to endometriosis, orofacial clefts, and stroke susceptibility 6. Intriguingly, DROSHA exhibits cytoplasmic localization in trophoblasts where it recognizes viral RNAs, suggesting antiviral defense functions beyond nuclear miRNA processing 4. These diverse functions underscore DROSHA's broad importance in gene regulation and disease pathogenesis.