ATP5MC1 (ATP synthase membrane subunit c locus 1) is a core component of mitochondrial Complex V (F₀F₁-ATP synthase), the enzyme responsible for ATP production from ADP 1. As part of the F₀ domain, ATP5MC1 forms a proton-conducting channel with subunit a (MT-ATP6), containing inlet and outlet half-channels that facilitate proton translocation from the intermembrane space into the matrix via a Grotthuss mechanism 1. This proton gradient drives a rotary catalytic mechanism in the F₁ head domain, coupling oxidative phosphorylation to ATP synthesis. ATP5MC1 expression is upregulated following acute aerobic exercise in skeletal muscle, reflecting enhanced mitochondrial oxidative capacity 2. The gene's glycine-rich domain is functionally critical, as mutations alter ATP synthase properties and permeability transition pore complex (PTPC) activity, exacerbating hypoxia/reoxygenation injury in cardiac myocytes 3. Multi-omics studies identify ATP5MC1 as putatively associated with sepsis pathogenesis, where reduced expression correlates with disease risk 4. In GFM1-deficient cells, ATP5MC1 upregulation suggests compensatory mitochondrial responses to impaired function 5. Network analyses highlight ATP5MC1 as a hub gene converging on mitochondrial metabolic pathways in paediatric asthma 6. These findings establish ATP5MC1 as essential for bioenergetics, cellular stress responses, and disease pathogenesis.