PBRM1 and renal cell carcinoma: We further discuss unresolved mechanistic paradoxes such as contradictory prognostic associations between HERV superfamily expression and PBRM1 inactivation in RCC, concluding with priorities for future research: validating HERV-derived neoantigens in immunotherapy platforms, optimizing epigenetic priming strategies to enhance viral mimicry effects, and establishing standardized HERV signatures as clinical biomarkers through multi-institutional cohorts.