Very recently, Colecraft and co-workers successfullydemonstrated that selective ubiquitin chain removal could rescue trafficking-deficientCFTR via the development of engineered DUBs (enDUBs).136 For this proof-of-concept study, they preparedan enDUB comprising the catalytic component of ubiquitin-specificprotease USP21 (enDUB-U21) and engineered CFTR protein to probe theimpact of six distinct CF-causing mutations of class II and classIV that all impair channel surface density. The gene discussed is CFTR; the disease is cystic fibrosis.