The study investigates the role of Ndufs4, an accessory subunit of mitochondrial complex I, in diabetic kidney disease (DKD). Using podocyte-specific Ndufs4 overexpression in mice, the researchers found that increased Ndufs4 expression improved mitochondrial morphology, dynamics, and albuminuria. They identified STOML2, a cristae shaping protein, as a key regulator linking NDUFS4 to improved mitochondrial function. Overexpression of NDUFS4 restored CI activity, mitochondrial respiration, and cristae integrity, while STOML2 knockout prevented these improvements. The findings suggest that targeting NDUFS4 could be a promising approach to slow DKD progression. The study highlights the importance of ETC integrity and NDUFS4 in maintaining mitochondrial function and preventing DKD progression.The study investigates the role of Ndufs4, an accessory subunit of mitochondrial complex I, in diabetic kidney disease (DKD). Using podocyte-specific Ndufs4 overexpression in mice, the researchers found that increased Ndufs4 expression improved mitochondrial morphology, dynamics, and albuminuria. They identified STOML2, a cristae shaping protein, as a key regulator linking NDUFS4 to improved mitochondrial function. Overexpression of NDUFS4 restored CI activity, mitochondrial respiration, and cristae integrity, while STOML2 knockout prevented these improvements. The findings suggest that targeting NDUFS4 could be a promising approach to slow DKD progression. The study highlights the importance of ETC integrity and NDUFS4 in maintaining mitochondrial function and preventing DKD progression.