CNNM2 encodes a divalent metal cation transporter mediating magnesium (Mg2+) homeostasis with substrate preference Mg2+ > Co2+ > Mn2+ > Sr2+ > Ba2+ > Cu2+ > Fe2+ 1. In the kidney's distal convoluted tubule, CNNM2 facilitates basolateral Mg2+ extrusion in a sodium-dependent manner, contributing to fine-tuning of systemic Mg2+ reabsorption 1. Mg2+ is essential for over 600 enzymatic reactions including energy metabolism and protein synthesis 2. CNNM2 mutations cause autosomal recessive hypomagnesemia with neurological manifestations 2. Beyond ion transport, CNNM2 emerges as a schizophrenia risk gene identified through genome-wide association studies 34. Reduced CNNM2 expression in prefrontal cortex impairs sensorimotor gating and cognition while altering dendritic spine morphogenesis in mice, supporting its neurobiological relevance 5. DNA methylation of CNNM2 is causally associated with schizophrenia in both brain and blood 6. CNNM2 variants also associate with hypertension risk in Chinese populations 7 and intracranial aneurysm susceptibility, particularly aneurysm rupture 8. These findings establish CNNM2 as functionally important for both metabolic Mg2+ homeostasis and neuropsychiatric disease pathogenesis.