ATG101 (autophagy related 101) is an essential component of the autophagy initiation machinery in mammalian cells. ATG101 functions as a critical subunit of the ULK1 kinase complex, which comprises ULK1, ATG13, FIP200, and ATG101, and represents the most upstream regulatory complex in autophagy 1. The primary function of ATG101 is to stabilize ATG13 by protecting it from proteasomal degradation, thereby maintaining the integrity of the autophagy initiation complex 12. ATG101 interacts with ULK1 in an ATG13-dependent manner and is essential for macroautophagy 1. Mechanistically, ATG101 contains a newly identified WF motif that facilitates recruitment of downstream autophagy proteins 2. Loss of ATG101 function results in defective autophagy processes, including both developmental and starvation-induced autophagy, leading to tissue homeostasis disruption in adult brains and midguts 3. ATG101 deficiency causes accumulation of ubiquitin-positive aggregates, shortened lifespan, and mobility defects 3. Clinically, ATG101 has emerged as a prognostic biomarker in hepatocellular carcinoma, where ATG101-related signatures correlate with patient survival and therapeutic responses 4. The conservation of ATG101 across eukaryotes, except in yeast which has a 'capped' ATG13 that doesn't require ATG101 for stabilization, highlights its fundamental importance in autophagy regulation 2.