ULK1 (unc-51 like autophagy activating kinase 1) is a serine/threonine protein kinase that serves as a master regulator of autophagy initiation in response to nutrient stress. Under nutrient-deficient conditions, AMPK directly phosphorylates ULK1 at Ser317 and Ser777, promoting autophagy activation 1. Conversely, under nutrient-rich conditions, mTOR phosphorylates ULK1 at Ser757, disrupting the ULK1-AMPK interaction and inhibiting autophagy 1. ULK1 functions upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate autophagosome formation and is essential for both general autophagy and specialized mitophagy pathways 2. The kinase plays distinct roles in different mitophagy contexts: AMPK activation enhances Parkin-mediated mitophagy of damaged mitochondria while simultaneously inhibiting NIX-dependent mitophagy of functional mitochondria through 14-3-3-mediated ULK1 sequestration 3. ULK1 deficiency leads to impaired mitophagy, resulting in accumulation of damaged mitochondria and aberrant p62 accumulation 2. In cancer contexts, ULK1 loss promotes breast cancer bone metastasis through defective mitophagy and NLRP3 inflammasome activation 4. Additionally, ULK1 mediates therapeutic effects in muscle atrophy through AMPK/ULK1-dependent autophagy enhancement 5.