biostudies-literatureUnknown22(1)Fernandez-Albarral JAHydrocephalus, characterized by ventriculomegaly due to cerebrospinal fluid accumulation in the cerebral ventricles, is a co-morbidity factor in several neurodevelopmental, psychiatric and neurodegenerative diseases. Aquaporin-4 (AQP4) is crucial for brain water homeostasis, with Aqp4 knockout mice showing sporadic ventriculomegaly and increased brain water content. Kinase D interacting substrate of 220 kDa (Kidins220), a transmembrane protein involved in neuronal survival, synaptic activity and neurogenesis, controls AQP4 levels in ependymocytes and brain astrocytes. Indeed, Kidins220 deficiency in mice leads to hydrocephalus by downregulating VPS35, a key component of the retromer complex, and targeting AQP4 to lysosomal degradation. Importantly, the ependymal barrier of idiopathic normaFluids and barriers of the CNS16https://www.ebi.ac.uk/biostudies/studies/S-EPMC11823095biostudies-literatureKidins220-deficient hydrocephalus mice exhibit altered glial phenotypes and AQP4 differential regulation in the retina and optic nerve, with preserved retinal ganglion cell survival.PMC11823095Pajuelo LSMElvira-Hurtado LSalazar JJSanz MSanchez-Puebla LLopez-Menendez CLopez-Cuenca ISanchez-Carralero MPIglesias TSalobrar-Garcia ERamirez JMFernandez-Albarral JAde Hoz RMatamoros JASimon-Garcia ARamirez AIfalseKidins220-deficient hydrocephalus mice exhibit altered glial phenotypes and AQP4 differential regulation in the retina and optic nerve, with preserved retinal ganglion cell survival.Hydrocephalus, characterized by ventriculomegaly due to cerebrospinal fluid accumulation in the cerebral ventricles, is a co-morbidity factor in several neurodevelopmental, psychiatric and neurodegenerative diseases. Aquaporin-4 (AQP4) is crucial for brain water homeostasis, with Aqp4 knockout mice showing sporadic ventriculomegaly and increased brain water content. Kinase D interacting substrate of 220 kDa (Kidins220), a transmembrane protein involved in neuronal survival, synaptic activity and neurogenesis, controls AQP4 levels in ependymocytes and brain astrocytes. Indeed, Kidins220 deficiency in mice leads to hydrocephalus by downregulating VPS35, a key component of the retromer complex, and targeting AQP4 to lysosomal degradation. Importantly, the ependymal barrier of idiopathic norma2025-01-01T00:00:00Z2025 Feb2025-04-25T17:42:55.183Z2025-04-06T06:48:17.459ZS-EPMC118230953993999010.1186/s12987-025-00626-z