SLC6A12 encodes a sodium- and chloride-dependent transporter that mediates cellular uptake of betaine and GABA, functioning in GABAergic neurotransmission and osmotic regulation. The transporter operates with a 3 Na+: 1 Cl−: 1 GABA coupling stoichiometry and facilitates GABA reuptake into presynaptic terminals, supporting GABA homeostasis under physiological conditions 1. SLC6A12 dysregulation is implicated in multiple diseases. In hepatocellular carcinoma, SLC6A12 is upregulated during lung metastasis and forms a positive-feedback loop with β-catenin whereby GABA binding stabilizes β-catenin to activate Wnt/β-catenin signaling, promoting metastatic progression 2. In ovarian cancer, aberrant hypomethylation of the SLC6A12 promoter drives 8.1- to 14.0-fold upregulation, with increased expression correlating with poor overall survival and enhanced cell migration and invasion 3. SLC6A12 overexpression in Parkinson's disease models impairs neuronal growth and promotes cell apoptosis through MAPK signaling pathway activation 4. In rheumatoid arthritis, high-salt diet exacerbates disease severity by promoting macrophage pyroptosis through sodium-dependent SLC6A12 activation of the SGK1/p38 MAPK/NF-κB axis 5. Genetic variants in SLC6A12 associate with negative symptoms in schizophrenia 6 and with aspirin-exacerbated respiratory disease susceptibility. SLC6A12 variants also emerge as potential therapeutic targets in Alzheimer's disease necroptosis subtypes 7.