Through activating the TDP43/Raptor/p62/Keap1/NRF2 axis, the reduction of Chchd10 in response to energy surplus awakens the adaptive response, which potentiates adipogenesis and GSTA4‐mediated 4‐HNE clearance to combat obesity. The gene discussed is RPTOR; the disease is obesity due to melanocortin 4 receptor deficiency.