Wdr77, also known as MEP50 or androgen receptor coactivator p44, is a WD-40 domain-containing protein and a crucial regulator of multiple cellular pathways [3]. It is often associated with protein arginine methyltransferase 5 (PRMT5) in histone methylation and is involved in pathways such as RIG-I-MAVS signaling, cell-cycle regulation, and apoptosis [1,3]. It plays an important role in processes like antiviral innate immune response, viral replication, and cancer progression [1,2,3]. Genetic models, especially knockout (KO) mouse models, are valuable for studying its functions.

In antiviral innate immunity, Wdr77 deficiency significantly potentiates the induction of antiviral genes upon negative-strand RNA virus infections, and myeloid-specific Wdr77-deficient mice are more resistant to RNA virus infection, indicating it negatively regulates the RIG-I-MAVS signaling pathway by inhibiting the prion-like aggregation of MAVS [1]. In cancer, germ-line loss-of-function variants in Wdr77 predispose to familial papillary thyroid cancer, and knockdown of Wdr77 in thyroid cancer cells leads to increased cell growth [4]. Also, in squamous cell carcinoma, depletion of PRMT5 and Wdr77 represses tumor growth in vivo, as they synergize to promote SCC proliferation via the ΔNp63α-p21 axis [5].

In conclusion, Wdr77 is a key regulator in multiple biological processes. Its functions in antiviral innate immune response and cancer progression are revealed through KO mouse models. Understanding Wdr77's role can provide new insights into the mechanisms of antiviral immunity and cancer development, potentially offering new strategies for disease treatment.