WWP1 is a HECT-family E3 ubiquitin ligase that regulates protein stability through polyubiquitination of diverse substrates 1. As an E3 ligase, WWP1 catalyzes ubiquitin transfer to targeted proteins, promoting their proteasomal degradation or modifying their function 2. WWP1 plays a critical role in the Hippo signaling pathway by monoubiquitinating AMOTL2, which facilitates LATS2 activation and YAP1 phosphorylation, ultimately repressing YAP1-driven transcription 3. Disease relevance is substantial across multiple contexts. In cardiac pathology, WWP1 elevation in heart failure promotes hypertrophy through K27-linked ubiquitination of DVL2, activating the DVL2/CaMKII/HDAC4/MEF2C pathway, making WWP1 inhibition a potential therapeutic strategy 2. In cancer, WWP1 exhibits context-dependent roles: it suppresses PTEN function through polyubiquitination, supporting tumorigenesis, while WWP1 inhibition reactivates PTEN as a tumor suppressor 4. WWP1 also promotes prostate cancer and esophageal cancer progression by facilitating CDKN1B and LATS1 degradation respectively, activating oncogenic pathways 5, 6. Clinically, WWP1 serves as both a prognostic marker and therapeutic target; small molecule inhibitors like indole-3-carbinol suppress cancer growth and promote bone fracture healing 4, 1.