FKBP6 (FKBP prolyl isomerase family member 6) is essential for male spermatogenesis and fertility. The protein functions as a co-chaperone that associates with HSP90 via its tetratricopeptide repeat (TPR) domain and plays a critical role in the piRNA (PIWI-interacting RNA) pathway 1. FKBP6 is required for piRNA biogenesis and amplification, delivering piRNAs to PIWI proteins like MIWI2 for transposable element silencing 1. Loss of FKBP6 function leads to derepression of LINE1 retrotransposons and reduced DNA methylation due to deficient nuclear accumulation of MIWI2 1. In humans, bi-allelic loss-of-function variants in FKBP6 cause severe spermatogenic failure, with affected individuals showing arrest at the round spermatid stage and producing no or extremely few sperm 2. Unlike mouse models, human FKBP6 deficiency severely impacts piRNA levels but does not increase LINE-1 expression 2. FKBP6 is also exploited by hepatitis C virus for replication, where it interacts with viral NS5A protein and forms complexes with other FKBP proteins 3. The gene is deleted in Williams-Beuren syndrome, though haploinsufficiency appears compatible with male fertility 4.