Shield-1 (Shld1) is a specific, cell-permeant and high-affinity ligand of FK506-binding protein-12 (FKBP), and reverses the instability by binding to mutated FKBP (mtFKBP), allowing conditional expression of mtFKBP-fused proteins. Shield-1 can stabilize proteins tagged with a mutated FKBP12-derived destabilization domain (DD).