NIPA2 is a highly selective magnesium ion transporter located in the plasma membrane that plays critical roles in cellular homeostasis and tissue development 1. The protein mediates intracellular magnesium levels, which regulate osteoblast function and bone metabolism 2. NIPA2 positively regulates osteogenic capacity through mitochondrial quality control, specifically via PINK1/Parkin-mediated mitophagy pathways and the PGC-1α/FoxO3a axis, particularly under high-glucose conditions characteristic of type 2 diabetes 3. NIPA2 also supports brain and muscle development and influences glucose-insulin metabolism and neurobehavioral outcomes 1. Deletion of the 15q11.2 BP1-BP2 region containing NIPA2 is associated with Burnside-Butler syndrome and more severe Prader-Willi syndrome phenotypes, with reported findings including developmental delay (73%), speech delays (67%), and motor impairment (42%) 45. Notably, CNV-related NIPA2 alterations show incomplete penetrance and variable expressivity 6. While magnesium dysmetabolism occurs with 15q11.2 deletions/duplications, urinary magnesium levels do not reliably predict CNV status 6. Additionally, NIPA2 serves as a cellular senescence regulator, with reduced expression correlating with senescence markers in vitro 7. NIPA2 represents a therapeutic target for type 2 diabetes osteoporosis management.