NIPA1 encodes a magnesium transporter protein with primary function in Mg(2+) ion transport across cell membranes, with secondary capacity to transport other divalent cations including Fe(2+), Sr(2+), Ba(2+), Zn(2+), and Co(2+) at reduced efficiency 1. The protein localizes to the plasma membrane and functions in transmembrane cation transport. NIPA1 supports critical physiological processes including brain and muscle development, glucose and insulin metabolism, and neurobehavioral outcomes 2. Pathogenic NIPA1 mutations cause spastic paraplegia type 6 (SPG6), an autosomal dominant hereditary spastic paraplegia (HSP) characterized by progressive lower extremity weakness and spasticity, often with adolescent-onset presentation 1. Specific mutations exhibit variable penetrance; the c.316G>A mutation associates with complex HSP including epilepsy and schizophrenia, while c.316G>C produces pure HSP, correlating with differential effects on protein expression 1. Beyond neurological disease, NIPA1 plays an unexpected role in cardiovascular health: the lncRNA NIPA1-SO suppresses NIPA1 expression and confers atherosclerotic protection through endothelial function modulation 3. Additionally, NIPA1 GCG repeat length does not appear to modify C9orf72-mediated ALS disease risk 4. SPG6 accounts for approximately 0.8% of HSP cases in population studies 1.