DIS3-like 3′–5′ exoribonuclease 2, DIS3L2, a member of the highly conserved RNase II/RNB family, attracted much research interest when, in 2012, Astuti and colleagues identified germline mutations in the DIS3L2 gene in patients affected by the Perlman syndrome, a congenital overgrowth condition associated with Wilms tumor susceptibility [1]. This evidence concerns the gene DIS3L2 and Nephroblastoma.