ATPAF1 (ATP synthase mitochondrial F1 complex assembly factor 1) is a nuclear-encoded mitochondrial chaperone protein essential for assembling the mammalian F1-F0 ATP synthase complex 1. The protein stabilizes the F1 sector during assembly, facilitating incorporation of F1-alpha and F1-beta subunits 2. ATPAF1 behaves as a maintenance gene with relatively constant expression across tissues 3. ATPA1 deficiency significantly impairs mitochondrial ATP synthase assembly and oxidative phosphorylation capacity. ATPAF1-knockout mice exhibit reduced F1 content, decreased ATP synthase dimers, mitochondrial ultrastructural abnormalities including cristae loss, and impaired cardiac function 1. At the cellular level, ATPAF1 deficiency triggers mitophagy dysregulation and impaired autophagy 1. Genetically, ATPAF1 variants associate with disease susceptibility across multiple conditions. Polymorphisms in ATPAF1 are associated with childhood asthma across diverse ancestries, with genome-wide significance achieved for specific SNPs 4, and ATPAF1 expression is elevated in asthmatic bronchial biopsies 4. ATPAF1 knockdown reduces prostate cancer cell growth under androgen-deficient conditions 5. Additionally, ATPAF1 expression is regulated by OGFOD1 during ischemic stress responses 6. These findings establish ATPAF1 as critical for mitochondrial bioenergetics and implicate it in complex disease pathogenesis.