SLC9A9 encodes a sodium/potassium-proton antiporter localized to recycling endosomes that regulates organellar pH by mediating electroneutral exchange of endosomal luminal H+ for cytosolic Na+ or K+ 1. By facilitating proton efflux, SLC9A9 counteracts V-ATPase-mediated acidification, thereby regulating endosome maturation and endocytic trafficking of plasma membrane receptors and neurotransmitters 2. The protein promotes transferrin receptor recycling to facilitate iron uptake and regulates synaptic transmission through axonal endosome pH control 1. SLC9A9 dysregulation associates with multiple neuropsychiatric disorders. Mutations in SLC9A9 affect calcineurin interaction and show age-dependent abnormal expression in ADHD rat models, suggesting a mechanistic link to ADHD pathophysiology 1. Genetic variants including rs9828519 dysregulate SLC9A9 expression in specific brain regions and associate with multiple sclerosis nonresponsiveness to interferon-beta treatment 3. Co-expression network analysis reveals SLC9A9 involvement in immune function, metabolism, apoptosis, and endocytosis relevant to autism spectrum disorder pathophysiology 2. Beyond neurology, SLC9A9 demonstrates oncogenic roles in colorectal, esophageal, and gastric cancers, correlating with EGFR signaling activation and worse prognosis 45. Genome-wide association studies identify SLC9A9 variants affecting plasma N-glycosylation, potentially through endosomal pH-dependent sialylation processes 6. These findings establish SLC9A9 as a multifunctional protein with therapeutic implications across neuropsychiatric and malignant diseases 7.