ATP5MC3 encodes a membrane subunit of mitochondrial ATP synthase (Complex V), which catalyzes ATP synthesis from ADP using the proton gradient generated by the electron transport chain. As part of the F₀ domain, ATP5MC3 participates in the c-ring that forms the rotary element coupling proton translocation to ATP production 1. ATP5MC3 variants cause variable neurologic phenotypes including early-onset dystonia, spastic paraplegia, developmental delay, and intellectual disability 12. De novo heterozygous missense mutations (p.Gly79Val, p.Asn106Lys) reduce Complex V activity and impair ATP generation and mitochondrial membrane potential 12. An autosomal dominant ATP5MC3 variant (p.Asn106Lys) segregates with spastic paraplegia and dystonia, likely through dominant-negative effects 2. Beyond neurologic disease, ATP5MC3 shows relevance to metabolic and degenerative conditions. Lower ATP5MC3 expression associates with reduced diabetic kidney disease risk, with downregulation observed in podocytes and tubular cells in diabetic kidneys 3. ATP5MC3 appears dysregulated in osteoporosis and various cancers, correlating with ferroptosis-related pathways 456. In Alzheimer's disease, ATP5MC3 is among ferroptosis-related targets potentially modulated therapeutically 7.