Slc39a5, also known as solute carrier family 39 member 5, is a zinc transporter that plays a vital role in regulating cellular zinc homeostasis. Zinc is an essential trace element involved in numerous cellular functions, and Slc39a5-mediated zinc regulation is associated with various biological pathways, including those related to extracellular matrix synthesis, cell proliferation, and angiogenesis [1,2,3].

In high myopia, Slc39a5 knockout (KO) human embryonic kidney cells (HEK293) show morphogenesis and migration abnormalities, along with significant injury to extracellular matrix (ECM) constituents. RNA-seq and qRT-PCR revealed decreased transcription of ECM-related genes (COL1A1, COL2A1, COL4A1, FN1, and LAMA1) in KO cells. The TGF-β signaling pathway, a regulator of ECM, was inhibited in Slc39a5-depleted cells, and this was due to insufficient zinc chelation destabilizing Smad proteins [1]. In lung adenocarcinoma, SLC39A5 overexpression promotes cell proliferation by accelerating the G1-to-S phase transition and inhibiting apoptosis, activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling. SLC39A5 knockdown inhibits tumorigenesis in a nude mouse xenograft model [2]. In zebrafish, knocking down slc39a5 expression using morpholino or CRISPR/Cas9-mediated gene editing leads to cardiac ischemia, abnormal red blood cell accumulation, and impaired venous angiogenesis, which can be restored by zinc chelation [3].

In conclusion, Slc39a5 is crucial for maintaining zinc homeostasis, which in turn impacts multiple biological processes. Studies using KO models have revealed its role in diseases such as high myopia, lung adenocarcinoma, and abnormal angiogenesis. These findings provide valuable insights into the molecular mechanisms underlying these diseases and suggest Slc39a5 as a potential therapeutic target [1,2,3].