CCDC88A (Girdin) is a multifunctional actin-binding protein that serves as a bifunctional modulator of heterotrimeric G proteins, acting as a guanine nucleotide exchange factor for Gi-alpha subunits and a guanine nucleotide dissociation inhibitor for Gs-alpha 12. The protein is essential for cell migration through its interaction with EGFR and regulation of PI3K-AKT signaling pathways 34. CCDC88A maintains actin cytoskeleton integrity and promotes formation of actin stress fibers and lamellipodia required for cell motility 56. In disease contexts, CCDC88A overexpression correlates with poor prognosis in pancreatic and hepatocellular carcinomas, where it promotes cell migration and invasiveness 78. The protein regulates cancer stemness through the miR-101/CCDC88A/VEGF axis 8, while in breast cancer, MSCs transfer CCDC88A to ER+ tumor cells via connexin-43-facilitated tunneling nanotubes, conferring drug resistance and enhanced dissemination 9. CCDC88A also facilitates HBV replication by enhancing endosomal trafficking and suppressing autophagic degradation of viral antigens 10. Loss-of-function CCDC88A variants cause PEHO-like syndrome, characterized by progressive encephalopathy, seizures, microcephaly, and cortical malformations 1112. Beyond neurodevelopmental disease, CCDC88A variants associate with alcohol use disorder and post-transcriptional regulation during human neurogenesis 1314.