Key observations were validated in db/db mice and primary proximal tubular epithelial cells (PTECs) exposed to high glucose with matched osmotic control.<h4>Results</h4>Genetically predicted higher <i>MLXIPL</i> expression was associated with increased T2D risk across multiple phenotype definitions and with higher UACR, including replication in non-diabetic individuals. Here, MLXIPL is linked to type 2 diabetes mellitus.