SCYL2, a member of the SCY1-like pseudokinase family, is evolutionarily conserved among eukaryotes. It plays crucial roles in multiple biological processes. In animals, it regulates secretory protein trafficking, especially in the nervous system where it suppresses excitotoxicity [2,3,6]. In plants, it is involved in phytosterol accumulation, plant growth, and development, as well as clathrin-mediated vesicle trafficking [1,4,7].

In mouse models, Scyl2 knockout leads to excess prenatal mortality, and surviving mice show severe neurological dysfunction, including degeneration of CA3 pyramidal neurons in the hippocampus due to a BAX-dependent apoptotic process triggered by excessive excitatory signaling [3]. In humans, bi-allelic loss-of-function variants in SCYL2 are associated with arthrogryposis multiplex congenita-4 (AMC4), characterized by severe arthrogryposis, corpus callosum agenesis, epilepsy, and often early death [2,5]. In plants, mutation of OsSCYL2 in rice affects photosynthesis, causes hypersensitive response-like cell death in a light-dependent manner, yet enhances resistance to bacterial pathogens [7].

In summary, SCYL2 is essential for normal functioning in both animals and plants. In animals, its loss-of-function is linked to severe neurological disorders like those seen in AMC4. In plants, it is involved in growth, development, and immunity. Studies using knockout models in mice and gene-editing in plants have significantly advanced our understanding of SCYL2's functions in these biological processes and associated disease or stress-related conditions.