DNAJC15 (Methylation-controlled J protein/MCJ) is a mitochondrial co-chaperone that functions as a negative regulator of oxidative phosphorylation and a component of the TIM23 translocase complex for mitochondrial protein import 1. It stimulates HSPA9 ATPase activity and prevents mitochondrial hyperpolarization, thereby restricting excessive ATP generation [UniProt Function]. Under cellular stress, DNAJC15 undergoes OMA1-mediated cleavage and subsequent degradation by AFG3L2, which impairs mitochondrial protein import and restricts OXPHOS biogenesis as an adaptive response 2. DNAJC15 plays critical roles in disease pathogenesis: reduced expression correlates with chemoresistance in ovarian and breast cancers through transcriptional repression by ETV7 3, while overexpression promotes ferroptosis sensitivity and restores cisplatin responsiveness in chemoresistant ovarian cancer cells 1. In brown adipose tissue, DNAJC15 loss enhances thermogenesis through eIF2α-mediated stress responses, independent of UCP1 4. Additionally, DNAJC15 regulates mitochondrial permeability transition pore opening through cyclophilin D coupling, modulating apoptosis induction 5. DNAJC15 was identified as a hub mitochondrial gene dysregulated in osteoarthritis 6 and as a novel metastasis-related protein in nasopharyngeal carcinoma 7, suggesting broad significance in metabolic diseases and cancer biology.