SEPHS1, or Selenophosphate Synthetase 1, is a gene encoding an enzyme that was initially thought to be involved in selenophosphate synthesis, which is crucial for selenoprotein biosynthesis [1,2,5]. Selenoproteins are vital for antioxidant defense, thyroid hormone metabolism, and cellular homeostasis [1]. Although phylogenetic analysis suggests SEPHS1 lost selenophosphate synthesis activity during evolution, it retains ATPase activity [2]. It is also implicated in the regulation of cellular redox homeostasis [2].

In various KO mouse models, SEPHS1 deficiency has shown significant impacts. In adult mice, cartilage-specific Sephs1 knockout causes aging-associated osteoarthritis and augments post-traumatic OA, due to impaired selenoprotein synthesis, elevated ROS levels, and chondrocyte senescence [3]. In mouse embryos, Sephs1 deficiency affects retinoic signaling and other related pathways, leading to embryonic lethality at E11.5 [2]. In mouse embryonic stem cells, Sephs1 KO shows little effect on pluripotency maintenance but impairs differentiation into three germ layers and gastruloid aggregation, especially cardiac differentiation [4].

In conclusion, SEPHS1 is essential for maintaining cellular redox homeostasis and plays a crucial role in multiple biological processes such as embryonic development, cartilage health, and stem cell differentiation. Studies using KO mouse models have revealed its significance in diseases like osteoarthritis and neurodevelopmental disorders, highlighting its potential as a therapeutic target [1,3,6].