Studies on podocytes from diabetic nephropathy mice suggest that specific Orai1 deletion prevents insulin-stimulated SOCE, slit-diaphragm disruption and proteinuria, possibly due to chronic stimulation of Orai1 activation or aberrant Ca2+ signaling, which in turn activates Ca2+-regulated phosphatases leading to remodeling of the actin cytoskeleton (Kim et al., 2021). Here, ORAI1 is linked to diabetic kidney disease.