USP21 and neoplasm: This review systematically summarizes the differential expression profiles of USP family members (e.g., USP1, USP3, USP7, USP8, USP9X, USP21, and USP22) in BTC and their clinical significance, with a focus on elucidating how specific USPs regulate tumor progression through key substrates, including poly(ADP-ribose) polymerase 1 (PARP1), dynamin-1-like protein (DNM1L), and O-GlcNAc transferase (OGT).