USP21 and cholangiocarcinoma: Based on these findings, future research should focus on the following directions: developing highly selective USP21 inhibitors to optimize targeted therapy for CCA; investigating the crosstalk between the USP21–HSP90 axis and immune checkpoints (e.g., PD-1/PD-L1) to explore novel combination immunotherapy strategies; and evaluating the synergistic effects of USP21 inhibitors with HSP90 inhibitors (e.g., Ganetespib) to overcome drug resistance and enhance therapeutic efficacy.