Magnesium transporter NIPA1 (NIPA1)

Magnesium transporter NIPA1 (NIPA1) is a transmembrane protein belonging to the SLC57 family that encodes a magnesium ion transporter with 329 amino acids and nine transmembrane domains. The protein plays a crucial role in regulating cellular magnesium levels, localizes primarily to early endosomes and the plasma membrane in neuronal and epithelial cells, and shows regulated surface expression in response to extracellular magnesium concentrations. NIPA1 also interacts with the type II BMP receptor, inhibiting BMP signaling important for neural development and axonal maintenance. Mutations, particularly polyalanine expansions, in NIPA1 are causative for hereditary spastic paraplegia type 6 and may contribute to amyotrophic lateral sclerosis risk. Extensive evidence points to its importance in normal neurologic development and function, although its direct therapeutic targeting remains investigational.

Other names

Non-imprinted in Prader-Willi/Angelman syndrome region protein 1Spastic paraplegia 6 proteinSLC57A1FSP3SPG6MGC35570Spastic paraplegia type 6 protein

Not therapeutically exploited to date. Theoretical mechanisms could include modulation of magnesium transport, or pharmacologic inhibition/activation based on inhibitory effect on BMP signaling.