As a crucial regulator of EGFR sorting and degradation, USP8 inhibition potently suppresses EGFR signaling (a promising strategy for EGFR-driven cancers) but may simultaneously induce epidermal and gastrointestinal toxicities, such as rash, itching, dry skin, oral mucositis, diarrhea, and anorexia. The gene discussed is EGFR; the disease is cancer.