DDX25 (DEAD-box helicase 25), also known as gonadotropin-regulated testicular RNA helicase (GRTH), is an ATP-dependent RNA helicase essential for male fertility. Primary function: DDX25 acts as a multifunctional post-transcriptional regulator of spermatogenesis 1. It transports target mRNAs from the nucleus to the cytoplasm for storage in chr11 bodies of spermatids 1, and associates with polyribosomes to regulate translation of spermatogenesis-related genes 2. Mechanism: DDX25 possesses inherent helicase unwinding and ATPase activities 1 and functions as an integral component of ribonuclear protein particles 1. Its expression is transcriptionally upregulated by gonadotropin and androgen 3. Disease relevance: DDX25 mutations cause non-obstructive azoospermia (NOA) and male infertility 4. A missense mutation (Arg242His) in infertile patients results in loss of phosphorylated GRTH expression, impairing protein function 5. Male mice lacking GRTH exhibit spermatogenic arrest with failure of round spermatid elongation and altered chr11 body structure 1. Notably, DDX25 also functions as a negative regulator of type I interferon pathway, facilitating RNA virus infection 6. Clinical significance: Genetic diagnosis of DDX25 defects can predict unsuccessful sperm retrieval in NOA patients, helping avoid unnecessary surgical intervention 4.