WSB1 (WD repeat and SOCS box containing 1) is a substrate-recognition component of an SCF-like E3 ubiquitin ligase complex that mediates ubiquitination and proteasomal degradation of target proteins 1. The protein recognizes diverse substrates including type II iodothyronine deiodinase (DIO2), HIPK2, VHL, and LRRK2, employing both canonical K48-linked ubiquitination and atypical K27/K29-linked chains for neuroprotection 12. WSB1 functions prominently in hypoxic responses as a HIF-1α target gene, where it stabilizes HIF-1α through VHL degradation while simultaneously protecting cells from apoptosis via HIPK2 degradation 13. In Parkinson's disease, WSB1 localizes to Lewy bodies and ubiquitinates mutant LRRK2 through non-canonical chains, promoting aggregation and conferring neuronal protection 2. Clinically, WSB1 dysregulation associates with multiple cancers: elevated expression correlates with poor prognosis in prostate and neuroblastoma, where specific isoforms (particularly WSB1 isoform 3) promote cell survival and chemoresistance 45. WSB1 contributes to cancer progression through HIF-1-dependent metabolic reprogramming and immune regulation 1. Additionally, WSB1 genetic variants associate with Th2-mediated immune responses in parasitic infections 6. Colorectal cancer exhibits WSB1-expressing malignant cell subtypes within tumor heterogeneity 7.