GMNC (geminin coiled-coil domain containing) is a master transcriptional regulator that controls multiciliated cell (MCC) differentiation and DNA replication initiation. GMNC functions as an evolutionarily conserved determinant of MCC fate, operating downstream of Notch signaling but upstream of Multicilin in the developmental hierarchy 1. Together with MCIDAS, GMNC forms a critical transcriptional network that activates key genes required for multiciliogenesis, including p73 and FOXJ1, which control centriole amplification and motile cilia formation 2. Loss of GMNC function prevents MCC differentiation in zebrafish and Xenopus embryos, while overexpression induces supernumerary MCCs 1. Clinically, GMNC disruption has significant disease relevance. The GMNC-MCIDAS program is critical for preventing choroid plexus carcinoma development, as NOTCH pathway activation in these tumors suppresses GMNC and MCIDAS expression, leading to multiciliation defects and increased tumor proliferation 3. GMNC variants are associated with Alzheimer's disease cerebrospinal fluid tau levels and brain glymphatic activity, suggesting roles in neurodegeneration and brain fluid clearance mechanisms 45. Additionally, GMNC is implicated in structural brain connectivity, particularly affecting neural cell proliferation and differentiation pathways 6.