GIMAP6, the GTPase of the immune-associated protein 6, is a gene crucial for autophagy, immune competence, and inflammation. It belongs to the GIMAP GTPases family, which is strongly expressed in the adaptive immune system. GIMAP6 is involved in pathways such as redox regulation, and its encoded protein may play a role in T-cell receptor signaling pathway, chemokine signaling pathway, and cytokine-cytokine receptor interaction [1,3].

In Gimap6-/-mice, there are defects in autophagy, redox regulation, and polyunsaturated fatty acid-containing lipids. Mice with deletion of Gimap6 within the T and B cell lineages show a 50-70% reduction in peripheral CD4+ and CD8+ T cells, along with autophagic disruption as indicated by increased levels of MAP1LC3B lipidated form and S405-phosphorylation of SQSTM1, and increased mitochondrial/cytoplasmic volume ratio and autophagosome numbers [1,2]. Gimap6-/-mice also die prematurely from microangiopathic glomerulosclerosis likely due to GIMAP6 deficiency in kidney endothelial cells [1]. In human patients with mutations in GIMAP6, there are infections, lymphoproliferation, autoimmunity, and multiorgan vasculitis, along with accelerated apoptosis [1,4].

In conclusion, GIMAP6 is essential for normal autophagic processes and the maintenance of a normal peripheral adaptive immune system. The study of Gimap6 knockout mouse models has revealed its crucial role in immune-related diseases, such as infections, autoimmunity, and multiorgan vasculitis, as well as in kidney-related pathologies like microangiopathic glomerulosclerosis [1,2,4].