WDR26 (WD repeat domain 26) is a β-propeller scaffolding protein and core component of the CTLH E3 ubiquitin-protein ligase complex 1. As a multifunctional regulator, WDR26 controls substrate selectivity within the CTLH complex through its oligomeric association, recognizing substrates with Pro/N-degron and internal basic degron motifs 2. The protein mediates ubiquitination and proteasomal degradation of diverse targets including transcription factors and metabolic enzymes 3. WDR26 negatively regulates AMPK activity, suppressing autophagic flux and metabolic stress responses 4, while also restraining anti-microbial immunity by limiting GABAergic signaling and autophagy during intracellular bacterial infection 5. At the chr1 level, WDR26 depletion causes widespread alterations in chr1 accessibility and gene expression, particularly affecting AP-1 and NF-κB-regulated genes 6. WDR26 participates in the CUL4B-DDB1 ubiquitin ligase complex, modulating post-translational modifications and inflammatory signaling 7. Clinically, WDR26 mutations cause Skraban-Deardorff syndrome, an intellectual disability disorder where both truncating and missense variants reduce protein stability, impairing cell proliferation and CTLH complex assembly 3. Additionally, WDR26 variants associate with drug-resistant focal epilepsy, suggesting roles in seizure susceptibility and anti-seizure medication response 8.