Based on limited published evidence, ZSWIM2 is an E3 ubiquitin-protein ligase that regulates death receptor-mediated apoptosis. The protein contains zinc-binding domains including a SWIM domain and functions with E2 ubiquitin-conjugating enzymes UBE2D1, UBE2D3, and UBE2E1 to promote Fas-, DR3-, and DR4-induced apoptosis 1. ZSWIM2 is testis-specific and can be epigenetically reactivated in colon cancer cells by DNA methyltransferase inhibitors 2, suggesting potential therapeutic implications.