The piRNA Ping-Pong pathway was first proposed from studies in "Drosophila" where the piRNA associated with the two cytoplasmic Piwi proteins, Aubergine (Aub) and Argonaute-3 (Ago3) exhibited a high frequency of sequence complementarity over exactly 10 nucleotides at their 5′ ends. This relationship is known as the "ping-pong signature" and is also observed in associated piRNA from Mili and Miwi2 proteins isolated from mouse testes. The proposed function of Ping-Pong in "Drosophila" or in mouse remains to be understood, but a leading hypothesis is that the interaction between Aub and Ago3 allows for a cyclic refinement of piRNA that are best suited to target active transposon sequences. Aub piRNA are primarily antisense to transposable element transcripts and are believed to be the main factor in targeting deleterious transcripts through complementarity. Conversely, Ago3 piRNA sequences are predominantly of sense orientation to transposable element transcripts and are derived from the product of Aub cleavage of transposon mRNA. As such, Ago3 piRNA lack the ability to target transposable element transcripts directly. Therefore, it was proposed that Ago3 piRNA guide the production of piRNA that are loaded into Aub by targeting newly exported piRNA cluster transcripts. Several lines of evidence support the effect of Ago3 on the production of Aub piRNA, in particular from examining the piRNA repertoire in "Drosophila" ovaries that are mutant for Ago3 and the Tudor-domain protein Kumo/Qin.