RNF5-IN-1 (FX12) is a selective RNF5 degrader. RNF5-IN-1 binds to RNF5 and inhibits its E3 activity, andpromotes proteasomal degradation of RNF5 in an endoplasmic reticulum (ER)-associated degradation (ERAD) way in cells. RNF5-IN-1 inhibits α-1-antitrypsin (NHK) dislocation with an IC 50 value of 2.7 μM. RNF5-IN-1 can be used for research of cystic fibrosis, acute myeloid leukemia, and certain viral infections.