GNA12 encodes a G protein alpha-12 subunit functioning as a molecular transducer in transmembrane signaling 12. Its primary role involves activating RhoA through RhoGEFs (ARHGEF12/LARG), which subsequently regulates transcription factor AP-1 and protein phosphatase 2A, controlling dephosphorylation of downstream targets 134. GNA12 inhibits CDH1-mediated cell adhesion independent of Rho activation and regulates CDH5 localization to the plasma membrane 56. It may modulate cell migration through TOR signaling 7. In cancer pathophysiology, GNA12 drives ovarian cancer progression by upregulating pro-tumorigenic networks involving AKT1, VEGFA, TGFB1, and STAT3 while downregulating growth-suppressive proteasome components 8. GNA12 promotes tumor cell invasion and metastasis via RhoA/ROCK signaling and pro-inflammatory cytokine production 9101112. GNA12 variants associate with normal pressure hydrocephalus risk, suggesting involvement in blood-brain barrier function 13. In hepatocytes, GNA12 activation increases glucose production through ROCK1-JNK signaling, with expression levels correlating with insulin resistance 14. Decreased GNA12 promoter methylation in preeclampsia associates with elevated mRNA expression 15. GNA12 overexpression in engineered exosomes reprograms glial cells toward neuroprotective phenotypes, promoting spinal cord repair 16.