ADAD2 (adenosine deaminase domain containing 2) is an RNA-binding protein essential for male fertility and spermatogenesis. The protein possesses double-stranded RNA adenosine deaminase activity and functions in adenosine-to-inosine RNA editing 1. ADAD2 displays high affinity for highly structured RNA substrates and remains immobile upon RNA binding, distinguishing it from other dsRNA-binding proteins 1. Mechanistically, ADAD2 mediates spermiogenesis—the differentiation of round spermatids into mature spermatozoa—through RNA processing and regulation of autophagy pathways 2. The protein interacts with DNAH17, a dynein arm protein critical for sperm motility 3. Pathogenic mutations in ADAD2 cause non-obstructive azoospermia (NOA) in humans. Biallelic missense and frameshift mutations disrupt protein expression or stability, resulting in severe spermiogenic failure and absence of sperm in ejaculates 2. Whole-exome sequencing studies identified ADAD2 variants in infertile cohorts at frequencies of 0.29-0.59%, with mutations associated with abnormal sperm ultrastructure and downregulation of DNAH17 expression 34. ADAD2 represents a validated genetic cause of male infertility with clinical diagnostic significance 5. Round spermatid injection (ROSI) using mutant Adad2 sperm can produce viable offspring, offering potential therapeutic approaches for affected males 2.