PIWI-L2 is a member of the PIWI subfamily of Argonaute proteins, evolutionarily conserved proteins containing both PAZ and Piwi motifs that are crucial for the biogenesis and function of small non-coding RNAs and play important roles in stem cell self-renewal, RNA silencing, and translational regulation in diverse organisms. PIWI-L2 has been implicated in multiple roles including stem cell self-renewal and is highly expressed in many breast cancers. In these tumors, PIWI-L2 silences the expression of STAT3, a regulator of Bcl-XL and cyclin D1, allowing the proliferation and survival of breast cancer stem cells. Recent studies have shown that overexpression of PIWI-like proteins are potential biomarkers for colon and other cancers.