YAP1 in control: how RNA networks and protein modifications shape its function and therapeutic targetability

YAP1 (Yes-associated protein 1), a central downstream effector of the Hippo signaling pathway, is tightly regulated through coordinated post-transcriptional and post-translational mechanisms. At the post-transcriptional level, expression stability and translational output of YAP1 are governed by competitive crosstalk among non-coding RNAs, modulation by RNA-binding proteins, and diverse mRNA modification processes. At the post-translational level, protein stability and subcellular distribution are finely controlled by an integrated modification landscape, including ubiquitination, acetylation, and SUMOylation. Functionally, YAP1 participates in senescence regulation, shapes the immune microenvironment through chemokine and immune checkpoint modulation, and drives metabolic reprogramming involving glucose, glutamine, and lipid pathways. Considerable advances have been achieved in therapeutic development directed at these regulatory axes, including disruption of YAP1-TEAD complex assembly, targeting of non-coding RNA-associated signaling cascades, and pharmacologic modulation of enzymes mediating post-translational modifications. Nonetheless, clinical translation remains constrained by limitations in drug selectivity, delivery efficiency, and the emergence of resistance. Subsequent investigations should prioritize refined molecular design, evaluation of rational combination regimens, and expanded clinical validation to accelerate the implementation of YAP1-oriented therapeutic approaches.