USP35 is a cysteine-type deubiquitinase that regulates protein stability across multiple cellular processes. Mechanistically, USP35 removes polyubiquitin chains from substrate proteins, stabilizing their expression and altering downstream signaling 1. Beyond well-established roles in cell cycle regulation via Aurora B stabilization and mitophagy, USP35 has emerged as a multi-functional oncogenic deubiquitinase with significant disease relevance. In cancer contexts, USP35 promotes tumorigenesis through distinct substrate-dependent mechanisms: it stabilizes ferroportin to inhibit ferroptosis in lung cancer 2, stabilizes Snail1 to enhance epithelial-mesenchymal transition in gastric cancer 1, stabilizes BRD4 to suppress ferroptosis in ER+ breast cancer 3, and maintains NRF2 and IAP protein levels to restrict apoptosis and ferroptosis in renal clear cell carcinoma 4. USP35 is significantly overexpressed in multiple cancer types and correlates with advanced disease stages and poor survival 5. Additionally, USP35 negatively regulates antiviral immunity by deubiquitinating MAVS and IRF3, suppressing inflammatory responses 67. Clinically, USP35 inhibition sensitizes cancer cells to chemotherapy and ferroptosis inducers, positioning it as a promising therapeutic target across multiple malignancies.