WDR54 (WD repeat domain 54) functions as an oncogene that regulates multiple signaling pathways involved in cancer progression. The protein plays a critical role in EGF receptor signaling, where it undergoes transglutaminase-mediated cross-linking to form dimers and trimers that regulate ERK pathway activity 1. When cross-linked, WDR54 colocalizes with EGF receptors in specific vesicles, sustaining receptor internalization and controlling degradation after EGF stimulation, thereby enhancing cellular proliferation 1. WDR54 is consistently overexpressed across multiple cancer types including colorectal cancer, head and neck squamous cell carcinoma, T-cell acute lymphoblastic leukemia, bladder cancer, and hepatocellular carcinoma 23456. The protein promotes tumor growth and metastasis through various mechanisms, including regulation of AKT and ERK signaling pathways 24, stabilization of MEMO1 protein to activate IRS1/AKT/β-catenin signaling 5, and enhancement of NF-κB signaling through interaction with RBBP5 6. High WDR54 expression correlates with poor patient prognosis and advanced tumor stages, making it a potential biomarker and therapeutic target 23. Additionally, rare deleterious variants in WDR54 are associated with reduced cell proliferation in induced pluripotent stem cells 7.