Phafin proteins, specifically Phafin1 and Phafin2, have recently emerged as critical players in cancer biology due to their involvement in essential cellular processes such as autophagy, apoptosis, and signal transduction. Phafin1, characterized by its pleckstrin homology (PH) domain and FYVE domain, regulates autophagy and apoptosis, thereby influencing cancer cell survival and proliferation. Dysregulation of Phafin1-mediated autophagy and its interaction with pro-apoptotic proteins like Bax contribute to apoptosis resistance in various cancers, including breast and lung cancer. Phafin2, sharing structural similarities with Phafin1, plays roles in endosomal trafficking and signaling pathways, enhancing cancer cell migration and invasion, particularly in colorectal and gastric cancers. Elevated levels of Phafin proteins correlate with poor prognosis and chemoresistance, underscoring their potential as diagnostic markers and therapeutic targets. Targeting Phafin proteins through small molecule inhibitors or monoclonal antibodies presents a promising therapeutic strategy, aiming to restore the balance between autophagy and apoptosis in cancer cells. This review synthesizes recent research on Phafin proteins, highlighting their molecular mechanisms, roles in specific cancers, and potential clinical applications, providing a comprehensive understanding of their significance in cancer biology and therapy.
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