Placenta associated 8 protein (PLAC8)

Placenta associated 8 protein (PLAC8) is a small, cysteine-rich lysosomal protein characterized by the PLAC8 domain, originally discovered in leukocyte inhibitory factor-regulated genes in the mouse uterus and placenta. It is critical for autophagosome-lysosome fusion, a key process in autophagy which is essential for metabolic homeostasis, especially in rapidly growing KRAS/p53 mutated pancreatic ductal adenocarcinoma cells. Beyond its role in cancer, PLAC8 also facilitates bactericidal actions in neutrophils and is implicated in brown fat differentiation, thermogenesis regulation, and defense response to bacterial infection. Pathological roles include its contribution to cancer progression, metabolic disorders, and certain retinal diseases. PLAC8 does not belong to widely defined receptor, transporter, enzyme, or transcription factor families but is instead classified by its motif and intracellular lysosomal function. Current research suggests it may offer a therapeutic window in cancer by selectively targeting autophagy-dependent tumors with minimal effects on normal tissues.

Other names

Placenta-specific gene 8 proteinPLAC8C15Protein C15DGICPNAS-144OnzinBM-004Down-regulated in gastrointestinal cancer protein

Inhibition of PLAC8 (genetic knockdown) suppresses tumor growth via blocking autophagic flux, impairing autophagosome-lysosome fusion. Potential mechanism for future targeted drugs is disruption of autophagy in KRAS/p53 mutant cancers.