The RBX1 RING domain (residues 40–108) was selected as the design target based on its established role as the catalytic subunit of SCF E3 ubiquitin ligase complexes. Literature mining and structural analysis (UniProt P62877, PDB 2LGV) identified the E2 ubiquitin-conjugating enzyme recruitment surface on helix α2 as the primary design epitope. Key hotspot residues were defined as W87, K89, R91, P95, and L96, validated by the natural inhibitor Glomulin (GLMN, K_d ≈ 36–45 nM), which competitively masks this surface. Critically, all targeted residues face outward from the CUL1-binding interface and are solvent-exposed in the free protein, making them accessible to exogenous binders.