The glymphatic system theory introduces a new perspective on fluid flow as well as homeostasis in the brain. Here, cerebrospinal fluid(CSF) in addition to interstitial fluid (CSFISF)moves from the perivascular spaces (PVS) of arteries to those of veins for drainage. Aquaporin-4 (AQP4) possesses a pivotal part in driving fluid amongst the PVS.The dysfunctional AQP4 is intricately correlated with the impairment of the glymphaticsystem. The working of the glymphatic system possesses lesser activity at the time of waking however is escalated at the time of sleep. The efficacy of the glymphatic system diminishes with escalation of age. Injury to the glymphatic system would ultimately result in to the generation along with propagation of plethora of brain diseases, for instance Alzheimer’s disease (AD),Parkinson’s disease (PD), chronic traumatic encephalopathy (CTE), as well as vasculardementia (VaD). Here, we reviewed earlier workcorrelated with theglymphatic system, inclusive of its ideas, fundamental, in addition to impacting factors.We posit that AQP4 possesses the capability of acting in the form of a target for the avoidance of in addition to therapy of certain brain diseases via the controlling ofthe glymphatic system. Previously we had detailed various etiopathogenesis ofAlzheimer’s disease (AD),Parkinson’s disease (PD),of NDD,here we add impairment of the glymphatic system as another etiologicalfactor.