PLAC8 (placenta associated 8) is a cysteine-rich protein that primarily functions as a regulator of autophagy and cellular survival pathways. The protein promotes autophagic flux by interacting with the VCP-UFD1-NPLOC4 complex to facilitate p53 degradation, thereby enhancing autophagy and inhibiting apoptosis 1. In trophoblast cells, PLAC8 upregulates autophagy-related genes including ATG5, ATG12, and Beclin-1, promoting cell viability and proliferation 2. PLAC8 serves as a specific marker for interstitial extravillous trophoblast cells (iEVTs), where it enhances invasion and migration by activating Cdc42 and Rac1 GTPases and inducing filopodia formation 3. The protein also functions as a critical host factor for SARS-CoV-2 viral entry, with overexpression boosting viral infection in lung cancer cells 4. Disease relevance includes elevated expression in pulmonary fibrosis, where PLAC8 overexpression attenuates fibrosis progression 1, and in preeclamptic placentas compared to normal pregnancies 5. In glioblastoma, aberrant PLAC8 expression mediates temozolomide resistance through AKT-mTOR signaling and promotes an immunosuppressive tumor microenvironment 6. PLAC8 also shows enriched expression in airway Th2 cells during allergic responses 7.