SLC45A1 encodes a proton-associated glucose transporter primarily localized to neuronal lysosomes in the brain 1. Beyond its canonical role in D-glucose transmembrane transport, SLC45A1 has a dual function: it mediates lysosomal sugar transport and stabilizes V1 subunits of the vacuolar H+-ATPase (V-ATPase) 12. Loss of SLC45A1 function causes lysosomal pH elevation and iron homeostasis disruption, subsequently impairing mitochondrial function 2. In glioblastoma, SLC45A1 deletion is the most significant truncal alteration associated with favorable mitochondrial subtype tumors relying on oxidative phosphorylation 3. SLC45A1 mutations cause intellectual developmental disorder with neuropsychiatric features, reclassified as a lysosomal storage disorder 12. Pathogenic variants reduce glucose transport activity (33-50% of wild-type function) 45 or disrupt protein localization to the cytomembrane 5. Notably, gain-of-function mutations disrupting DNA G-quadruplex structures elevate SLC45A1 expression, also causing developmental disorder 6. Clinical presentations include moderate to severe intellectual disability, epilepsy, and variable neuropsychiatric features 4. SLC45A1 represents the second cerebral glucose transporter implicated in neurodevelopmental disease after GLUT1 4.