PHAF1 (phagophore assembly factor 1), also designated MYTHO (macro-autophagy and youth optimizer), is a FoxO-dependent autophagy regulator that plays a critical role in skeletal muscle homeostasis 1. PHAF1 functions as a regulatory component of the autophagy machinery, associating with autophagosome formation sites in complex with BCAS3 during both selective and non-selective autophagy. At the molecular level, PHAF1 serves as a biomarker for macroautophagy activation, with elevated expression correlating positively with LC3B-II:LC3B-I ratios during high-intensity exercise 2. PHAF1 expression is tightly regulated and upregulated in catabolic conditions including fasting, denervation, cachexia, and sepsis 1. While moderate PHAF1 upregulation supports adaptive autophagy responses to exercise 2, excessive or prolonged PHAF1 downregulation causes severe myopathy characterized by impaired autophagy, mTORC1 hyperactivation, muscle weakness, and ultrastructural degeneration 1. Conversely, PHAF1 overexpression is sufficient to induce muscle atrophy, positioning it as a critical rheostat controlling muscle mass balance 1. The mTORC1 inhibitor rapamycin partially rescues PHAF1-deficiency phenotypes, suggesting therapeutic potential. Additionally, PHAF1 is identified as a candidate gene for skeletal muscle remodeling in response to high-intensity interval exercise 3, highlighting its broader role in exercise-induced adaptation.