Notably, post-translational modifications (ubiquitination, acetylation, SUMOylation) of pathway components dynamically regulate the stability and activity of downstream effectors YAP/TAZ, whose sustained activation through molecular aberrations drives tumor progression and treatment resistance in head and neck malignancies.The pathway’s extensive crosstalk with Wnt signaling, NF-κB cascades, and estrogen receptor networks creates context-dependent regulatory plasticity that contributes to tumor heterogeneity. The gene discussed is ESR1; the disease is neoplasm.