TDRKH (tudor and KH domain containing) is an RNA-binding protein with critical roles in germline development and piRNA biogenesis. The protein contains one tudor domain and two KH domains that mediate RNA or single-strand DNA binding 1. TDRKH participates in primary piRNA processing, catalyzing the conversion of 31-37 nucleotide intermediates into mature piRNAs through its localization to pi-bodies and piP-bodies 2. This function is essential for repressing transposable elements during spermatogenesis and meiosis, thereby maintaining germline integrity 3. TDRKH mutations cause non-obstructive azoospermia (NOA) in humans. Biallelic TDRKH variants were identified in NOA patients with error-prone meiosis and spermatogenic arrest, demonstrating that defects in piRNA-processing genes universally result in unsuccessful sperm retrieval 3. Reduced TDRKH expression accompanies PNLDC1 mutations, indicating coordinate dysfunction in the piRNA processing pathway impairs male fertility 2. Beyond reproductive function, TDRKH has been implicated in hereditary motor neuropathy pathogenesis 4 and identified as a putatively causal protein in asthma risk through genetic proteomics analysis 5. Additionally, TDRKH-AS1, an antisense lncRNA, promotes breast cancer progression and preeclampsia pathology through distinct molecular mechanisms 6, 7.