Wdr54, a member of the WD40 repeat (WDR) domain-containing protein family, has emerged as an important gene in multiple biological processes and disease conditions. The WD40 repeat domains are known to be involved in various protein-protein interactions, which likely contribute to Wdr54's functions. It may participate in pathways related to cell growth, survival, and metastasis, and is of great significance in understanding cancer development and sperm-oocyte fusion [2,5,6].

In cancer research, studies have shown that Wdr54 is overexpressed in multiple cancers. In T-cell acute lymphoblastic leukemia (T-ALL), depletion of Wdr54 inhibited cell viability, induced apoptosis, and arrested the cell cycle at the S phase, impeding leukemogenesis in a xenograft model. The mechanism may involve down-regulating the expression of PDPK1, phospho-AKT (p-AKT), total AKT, phospho-ERK (p-ERK), Bcl-2 and Bcl-xL, while up-regulating cleaved caspase-3 and cleaved caspase-9. RNA-seq analysis also indicated its role in regulating some oncogenic genes in multiple signaling pathways [1]. In bladder cancer, Wdr54 promoted tumorigenesis, metastasis, and impaired chemosensitivity by preventing the degradation and ubiquitination of MEMO1, promoting the interaction between MEMO1 and IRS1, and activating the IRS1/AKT/β-catenin pathway [4]. In colorectal cancer, knockdown of Wdr54 significantly inhibited cell growth and aggressiveness, and high Wdr54 expression was an independent risk factor for disease-specific survival [5]. In head and neck squamous cell carcinoma (HNSCC), Wdr54 was overexpressed, and its expression increased with disease progression, was associated with metastasis, and patients with high levels had a poorer prognosis [3].

In conclusion, Wdr54 plays oncogenic roles in multiple cancers, affecting cell growth, survival, and metastasis through various signaling pathways. Although no KO/CKO mouse models were mentioned in the provided references, the in vitro and in vivo xenograft studies have clearly demonstrated its significance in cancer-related biological processes. Understanding Wdr54 may provide potential therapeutic targets for these cancers. Additionally, its role in sperm-oocyte fusion reveals its importance in reproductive biology [1,3,4,5,6].