TMEM70 functions as a scaffold protein essential for mitochondrial ATP synthase (complex V) biogenesis, specifically facilitating the assembly of the c-ring component 12. The protein participates in the early stages of ATP synthase assembly by promoting membrane insertion and oligomer formation of subunit c/ATP5MC1 through direct interactions 31. TMEM70 forms large oligomeric scaffolds within mitochondrial cristae membranes, where it provides a platform for gradual c-ring assembly by interacting with subunit c molecules not yet incorporated into mature ATP synthase complexes 1. The protein also protects subunit c from intramitochondrial proteolysis 43. Additionally, TMEM70 binds to complex I and contributes to the stability of its membrane-bound subassemblies 2. TMEM70 is synthesized as a 29kDa precursor and processed to a 21kDa mature form localized to the inner mitochondrial membrane 4. Mutations in TMEM70 cause mitochondrial complex V deficiency, nuclear type 2, presenting as severe early-onset mitochondrial encephalo-cardiomyopathy with cardiomyopathy being a frequent manifestation 56. TMEM70 deficiency represents one of the most common nuclear genetic defects affecting ATP synthase 76.