ATP5MK encodes subunit k of the mitochondrial ATP synthase complex (Complex V), a critical component of the F₀ domain that catalyzes ATP synthesis from ADP using the proton gradient generated by the electron transport chain. ATP5MK is essential for dimerization of the ATP synthase complex, a requirement for efficient ATP synthesis in mitochondria 1. The protein functions as part of the integrated membrane-proton channel system, where the rotary mechanism of the central stalk couples proton translocation to ATP production in the catalytic F₁ domain. Biallelic mutations in ATP5MK cause Mitochondrial Complex V Deficiency, Nuclear Type 6 (MC5DN6), a progressive autosomal recessive neurodegenerative disorder characterized by developmental regression, intellectual disability, muscle weakness, spasticity, and abnormal gait patterns, typically manifesting in early childhood 2. A splice-site founder mutation (c.87+1G>C) in Ashkenazi Jewish populations causes Leigh syndrome by impairing Complex V dimerization and reducing ATP synthesis rates 1. Additionally, ATP5MK expression is altered in the placenta following prenatal cannabinoid exposure, suggesting potential involvement in neurodevelopmental risk pathways associated with schizophrenia 3. Clinically, ATP5MK represents a rare but important diagnostic target for patients with early-onset neurodegenerative disease, as genetic testing can enable early diagnosis of this severe mitochondrial disorder.