The Kidins220–SNX27–retromer–AQP4 pathway was discovered as a regulatory mechanism for brain AQP4 expression and its participation in brain ventricular enlargement and hydrocephalus by Puerto et al. We detected an unexpected relationship between SNX27-retromer downregulation and AQP4 lysosomal degradation caused by the loss of Kidins220, as well as a dramatic drop in Kidins220 and AQP4 expression at the ependymal barrier in patients with iNPH (Del Puerto et al., 2021). The gene discussed is AQP4; the disease is Hydrocephalus.