WSB2 (WD repeat and SOCS box containing 2) functions as a substrate-recognition component of CRL5 (Cullin 5-RBX2-Elongin B/C) E3 ubiquitin ligase complexes, mediating the ubiquitination and proteasomal degradation of specific target proteins 1. The protein plays critical roles in apoptosis regulation by targeting NOXA, a pro-apoptotic BCL-2 family protein, for degradation through its E3 ligase activity 1. In hepatocellular carcinoma, WSB2 promotes tumorigenesis by degrading wild-type p53 through K48-linked polyubiquitination at Lys291 and Lys292 sites, subsequently activating the IGFBP3-AKT/mTOR signaling pathway 2. WSB2 demonstrates tissue-specific expression patterns during development, showing male-specific expression in embryonic gonads and presence in Sertoli cells and germ cells throughout spermatogenesis 3. In melanoma, WSB2 promotes cell proliferation, cycle progression, and migration through regulation of c-Myc, β-catenin, and cell cycle proteins including CDK4 and Cyclin D3 4. Loss-of-function mutations in WSB2 cause a neurodevelopmental syndrome characterized by developmental delay, microcephaly, and brain structural abnormalities 5. Pan-cancer analysis reveals variable WSB2 expression across tumor types, with overexpression associated with poor prognosis in several malignancies 6.