Macroautophagy (hereafter autophagy) is a primarily degradative pathway that plays critical roles in cellular homeostasis 1. The morphological and functional hallmark of autophagy is the double-membrane autophagosome, a sequestering compartment that is derived from the phagophore. One of the key components of the protein machinery that drives autophagy is BECN1, the product of the BECN1 gene and the homolog of yeast Vps30/Atg6. There are two phosphatidylinositol 3-kinase (PtdIns3K) complexes in yeast, both of which contain the PtdIns3K Vps34, the presumed regulatory subunit Vps15, and Vps30/Atg6 2. Complex I also includes Atg14, and is specific to autophagy, whereas this component is replaced in complex II by Vps38, which functions in endosomal trafficking. BECN1 is part of at least three class III PtdIns3K complexes in mammals 3 that also include the PtdIns3K PIK3C3/VPS34, PIK3R4/VPS15, and different combinations of ATG14/ATG14L/BARKOR, UVRAG, AMBRA1 and/or KIAA0226/RUBICON. The ATG14-containing complex acts at an early stage of autophagosome formation, whereas UVRAG (which binds BECN1 at the same domain) directs the complex to act at a later stage of autophagosome maturation and also participates in endocytic trafficking. KIAA0226/RUBICON localizes the PtdIns3K complex to late endosomes/lysosomes and acts to inhibit autophagy. The PtdIns3K complex plays a critical role in autophagy by synthesizing PtdIns3P, a phosphoinositide that recruits certain autophagy-related (ATG) proteins to the site of phagophore formation. BECN1 in particular has been the subject of much research, stemming in part from its identification as a tumor suppressor that is mutated in several human cancers. In addition to its autophagic function as a component of the PtdIns3K complex, BECN1 is connected to the apoptosis pathways via its ability to bind to antiapoptotic factors such as BCL2, BCL2L1/Bcl-XL and related proteins. A critical point regarding its function is that BECN1, along with AMBRA1 4, may act as part of a balance point that controls the cellular response to stress, dictating whether the outcome is cytoprotective or results in cell death; for example, the BCL2-BECN1 complex inhibits autophagy and favors apoptosis. Accordingly, several regulatory molecules modulate autophagy through posttranslational modification of BECN1 or BCL2, including DAPK1 5 and MAPK8/JNK1 6. Furthermore, BECN1 may also contribute to apoptosis following caspase cleavage and mitochondrial translocation 7, whereas the endoplasmic reticulum-localized population of BECN1 is involved in promoting autophagy 8.