Slc30a1, also known as zinc transporter ZnT1, is a crucial gene encoding a ubiquitous zinc efflux transporter. It plays a vital role in maintaining cellular and systemic zinc homeostasis. Zinc is essential for various cellular processes such as proliferation, survival, and the regulation of numerous physiological functions. Genetic models, like gene knockout mice, have been instrumental in studying Slc30a1's function.

Intestinal Slc30a1 knockout mice demonstrated its critical role in survival, safeguarding intestinal barrier integrity and systemic zinc homeostasis. Its localization to the basolateral membrane of intestinal epithelial cells was revealed through lineage tracing [2]. In macrophages, Lyz2-Cre-driven Slc30a1 conditional knockout mice showed increased susceptibility to Salmonella infection. Slc30a1-deficient macrophages had defective intracellular killing, reduced activation of nuclear factor kappa B, and decreased nitric oxide production, along with intracellular zinc accumulation [3]. In zebrafish, slc30a1a and slc30a1b double mutants had increased melanocytes, and genes in the melanoma pathway and mt2 were upregulated. Elevated zinc levels from Slc30a1 deficiency promoted melanocyte proliferation [4]. Also, Slc30a1-deficient zebrafish had zinc accumulation in neural crest cells, with changes in the expression of stemness markers and pharyngeal arch dorsal genes, and knocking down snai2 or jag1b rescued pharyngeal arch development [5].

In summary, Slc30a1 is essential for maintaining zinc homeostasis across different cell types and organisms. Studies using KO/CKO mouse models and zebrafish mutants have revealed its role in processes like survival, host defense, melanocyte development, and pharyngeal arch differentiation. Understanding Slc30a1's function can provide insights into diseases related to zinc dysregulation, such as primary aldosteronism where somatic SLC30A1 mutations can cause aldosterone-producing adenomas [1].