Tdrd5, a member of Tudor domain-containing proteins (TDRDs), has been implicated in the P-element-induced wimpy testis-interacting RNA (piRNA) pathway. Tudor family proteins, including Tdrd5, recognize and bind to proteins with methylated arginine or lysine residues, playing roles in many cellular processes. Tdrd5 is of great importance in germ cell development across different species [1].

In mice, conditional inactivation of Tdrd5 in postnatal germ cells shows it is essential for pachytene piRNA biogenesis, selectively regulating the production of pachytene piRNAs from abundant precursors [2]. Tdrd5-deficient males are sterile due to spermiogenic arrest at the round spermatid stage, with disorganized intermitochondrial cements (IMCs) and chromatoid bodies (CBs), and failure to repress LINE-1 retrotransposons [4]. In humans, homozygous deleterious variants in the C-terminal of Tdrd5 impair spermiogenesis, causing severe oligoasthenoteratozoospermia [3]. In locusts, knockdown of LmTdrd5 (the Tdrd5 ortholog) leads to problems in spermatogenesis and oogenesis, affecting germ cell development and fertility [1].

In conclusion, Tdrd5 is crucial for germ cell development and fertility, playing essential roles in processes like piRNA biogenesis, retrotransposon silencing, and chromatoid body assembly. Studies on Tdrd5 knockout mouse models and loss-of-function experiments in other species have revealed its significance in male infertility, providing insights into the underlying mechanisms and potential treatment strategies for related diseases [1,2,3,4].