Zcchc3, a zinc-finger protein, is crucial in the innate immune response. It functions as a positive regulator in multiple immune-related pathways such as those mediated by retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), cyclic GMP-AMP synthase (cGAS), and Toll-like receptor 3 (TLR3) [1,3,6,8]. It also plays a role in suppressing retrotransposition of LINE-1, an autonomous non-LTR retrotransposon [2,4]. Zcchc3 is involved in the pathophysiology of triple-negative breast cancer and restricts the infection and production of viruses like HIV-1 and PEDV [5,7,9]. Genetic models, especially KO/CKO mouse models, are valuable for studying its functions.

Zcchc3-deficient mice are more susceptible to RNA virus, DNA virus, and herpes simplex virus type 1 or vaccinia virus infection, indicating its importance in innate immune responses against these viruses [1,8]. In contrast, Zcchc3 -/- mice are more resistant to poly(I:C)-induced inflammatory death, suggesting its role in TLR3-mediated signaling [3]. In triple-negative breast cancer, ZCCHC3 silencing repressed the proliferation of TNBC cells in vitro and in vivo, showing its involvement in cancer progression [7].

In summary, Zcchc3 is essential for innate immune responses against various viruses and plays a role in retrotransposon control and cancer pathophysiology. The use of KO/CKO mouse models has significantly contributed to understanding its functions in these disease-related areas, providing insights into potential therapeutic strategies for viral infections and cancer.