Tandem Ubiquitin Binding Entities (TUBEs) have become essential tools for ubiquitin research due to their extremely high affinity for K48‑ and K63‑linked tetra‑ubiquitin, binding 100–1000 times more tightly than monomeric UBAs. They also protect polyubiquitinated proteins from DUBs and the proteasome, enabling efficient isolation of native polyubiquitin chains from cells and tissues under mild conditions. TUBE1 and TUBE2 enrich all ubiquitin linkage types, making them ideal when the linkage is unknown. K48 TUBE HF provides strong selectivity for K48‑linked chains and can be paired with K63 or M1 (linear) TUBEs to study linkage architecture in target proteins. Together, TUBEs offer a powerful platform for isolating, enriching, and characterizing polyubiquitinated proteins.