To further explore mechanisms underlying the T2D-protective role of zinc and identify additional genetic determinants influencing systemic zinc homeostasis, we tested loss-of-function variation in zinc transporters for association with circulating zinc and T2D risk and identified rare putative LOF (pLOF) variants (MAF <1%) in SLC39A5 associated with elevated circulating zinc (p=4.9 × 10–4). Here, SLC39A5 is linked to type 2 diabetes mellitus.