Post-translational modifications in retinoblastoma: mechanisms, immune regulation, and therapeutic opportunities.

Retinoblastoma is an early-childhood retinal malignancy driven predominantly by biallelic RB1 inactivation and consequent RB-E2F checkpoint deregulation. Post-translational modifications (PTMs) add a rapid, reversible regulatory layer that rewires RB-centered signaling, chromatin control, metabolic adaptation, and therapy resistance. This review summarizes PTM mechanisms relevant to retinoblastoma, highlighting phosphorylation- and ubiquitination-centric circuits, as well as acetylation and methylation that modulate RB pathway function and downstream oncogenic phenotypes. We discuss actionable therapeutic opportunities, including compounds and degraders targeting PTM enzymes, and emphasize underexplored modifications such as SUMOylation, lactylation, and glycosylation that warrant systematic investigation in retinoblastoma. Finally, we integrate PTM biology with emerging immunotherapies and propose rational PTM-immunotherapy combinations and biomarker-guided translation to improve durable eye salvage and metastatic control.